Conditions: Metastatic Castration-resistant Prostate Cancer Metastatic Castration-sensitive Prostate Cancer Metastatic Prostate Cancer
Keywords: Prostate Metastatic Cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 107
Healthy volunteers: no

Brief summary:
The purpose of this study is to investigate the safety and efficacy of a new formulation of an existing drug product called TAVT-45 in patients with metastatic prostate cancer.

Detailed description:
This is a Phase 3 randomized, open-label study to evaluate the pharmacodynamic effect and safety profile of TAVT-45 compared to Zytiga (reference abiraterone acetate formulation, hereafter referred to as R-AA) in patients with high-risk metastatic castrate sensitive prostate cancer (mCSPC) and metastatic castrate resistant prostate cancer (mCRPC). Randomization was stratified by prostate cancer population (CSPC vs CRPC) and baseline testosterone (\<10 vs ≥ 10 ng/dL). Patients were treated for 84 days and randomized into one of two groups in a 1:1 ratio:

* TAVT-45: Administered twice daily as 1 x sachet containing TAVT-45 (250 mg abiraterone acetate), reconstituted in water or specified fruit juice (orange juice), + Prednisone (5 mg once or twice daily, depending on prostate cancer population)
* R-AA: Administered once daily as (2 x 500 mg Zytiga tablets) + Prednisone (5 mg once or twice daily, depending on prostate cancer population)

Arms:
arm 1: TAVT-45 administered twice daily as a 1 x sachet containing TAVT-45 (250 mg abiraterone acetate) + Prednisone (5mg once or twice daily, depending on prostate cancer population). TAVT-45 administered approximately every 12 hours without respect to food. Patients treated for 84 days. arm 2: Zytiga (reference abiraterone acetate formulation, hereafter referred to as R-AA) administered once daily as (2 x 500mg Zytiga tablets) + Prednisone (5mg once or twice daily, depending on prostate cancer population). R-AA administered once daily either ≥ 1 hour before or ≥ 2 hours after a meal. Patients treated for 84 days.

Interventions: intervention 1: TAVT-45 intervention 2: Zytiga intervention 3: Prednisone
Intervention descriptions: intervention 1: 250 mg abiraterone acetate granules for oral suspension in a sachet, reconstituted in water or specified fruit juice (orange juice), administered twice daily. intervention 2: 500 mg tablet, two tablets administered once daily intervention 3: mCSPC patients received 5 mg orally once daily. mCRPC patients received 5 mg orally twice daily.

Protocol document:
Prot_SAP_000.pdf: 
 
  
 
 
 
TAVT-45 (abiraterone acetate) Granules for Oral Suspension  
 
Clinical Trial Protocol TAVT45C02 
 
Phase 3 study investigating the efficacy and safety of TAVT-45 (abiraterone acetate) Granules 
for Oral Suspension (a novel abiraterone acetate formulation) relative to a reference 
abiraterone acetate formulation in patients with 
metastatic Castrate Sensitive Prostate Cancer (mCSPC) and metastatic  
Castrate Resistant Prostate Cancer (mCRPC)  
Document Type: 
 
Clinical Trial Protocol 
Sponsor Study Number:      
TAVT45C02  
IND Number:  
 
139118 
 
EudraCT Number: 
 
2020-005611-46 
 
Version Number: 
 
3.0 
 
Clinical Trial Phase: 
 
3 
 
Date of Protocol: 
 
26 Mar 2021 
 
Sponsor: 
 
 
 
Tavanta Therapeutics, Inc. 
101 E. Baltimore Ave, # 602  
Media, PA 19063  
Tel: +1 833 776 8963 
  
Property of Tavanta Therapeutics, Inc. 
Confidential  
May not be used, divulged, published, or otherwise disclosed without 
the consent of Tavanta Therapeutics, Inc.  
 
Clinical Trial Protocol Version 3.0 


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Study Contacts 
 
 
Clinical CRO: 
TMC Pharma Services Ltd. 
 
Lodge Farm Barn 
 
Elvetham Park Estate 
 
Fleet Road 
 
Hartley Wintney, Hants RG27 8AS, UK 
 
 
Central Laboratory: 
Covance Central Laboratory 
 
7 rue Marcinhes 
 
1217 Geneva 
 
Meyrin Switzerland 
 
Phone 41 58 822 7000 
 
Fax: 41 48 822 6999 
 
 
Covance Inc.  
 
8211 SciCor Drive 
 
Indianapolis, IN 46214 
 
Phone: 317 271 1200 
 
Fax: 317 273 4030 
 
Bioanalytical Laboratory: Covance Inc.  
 
8211 SciCor Drive 
 
Indianapolis, IN 46214 
 
Phone: 317 271 1200 
 
Fax: 317 273 4030             
 
Medical Monitor: 
Dr Peter Hession 
 
Email:  TavantaMedical@tmcpharma.com  
 
24/7 support: +44 (0) 125 284 2255 
 
Pharmacovigilance: 
TMC Pharma Ltd. 
 
Email: tavanta@tmcpharma.com  
 
EU Fax: +44 (0) 118 900 7822 
 
US Fax: +1 617 66 36 222 
 
 
 


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Signatures for Investigators 
 
CONFIDENTIALITY AND GCP COMPLIANCE STATEMENT 
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, and 
any other drug information provided by the sponsor. I agree to conduct this study in 
accordance with the requirements of this protocol and also protect the rights, safety, privacy, 
and well-being of study patients in accordance with the following: 
• The ethical principles that have their origin in the Declaration of Helsinki. 
• International Council for Harmonisation E6 Good Clinical Practice: Consolidated 
Guideline. 
• All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations. 
• Regulatory requirements for reporting serious adverse events defined in Section 7 of this 
protocol. 
Information taken from the study protocol may not be disseminated or discussed with a third 
party without the express consent of the sponsor.  
 
 
 
 
 
 
 
Principal Investigator Name 
 
Signature 
 
 
 
 
 
Date 
 
 
 
 
 
 
 


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Signatures for Sponsor  
 
 
 
 
Elizabeth Duus, PhD 
 
Executive Director, Clinical Development 
Signature 
Tavanta Therapeutics, Inc. 
 
 
Date 
 
 
 
Dominic Capone 
 
Senior Director, Clinical Development 
Signature 
Tavanta Therapeutics, Inc. 
 
 
Date 
 
 
 
Signatures for CRO  
 
Tomasz Knurowski, MD 
 
Chief Medical Officer 
Signature 
TMC Pharma. 
 
 
Date 
 
 
 
 
 
 
 
 


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Summary of Revision History 
 
Document Status  
Version Date  
Summary of Key Changes  
Version 1.0  
(final protocol) 
01 Dec 2020 
• 
Not applicable 
Version 2.0 
(amendment 1) 
28 Jan 2021 
• 
Section 5.6.5 (Permitted dose adjustments and 
interruptions of study treatment):  added text 
to provide guidance on toxicity management 
during this study related to hepatotoxicity and 
Grade ≥ 3 toxicities, in alignment with Zytiga 
prescribing information 
• 
Section 5.6.9 (Discontinuation of study 
treatment):  added text to clarify that ALT or 
AST rises above 5x ULN, or total bilirubin 
rises above 3x ULN, at any time during the 
study will result in permanent discontinuation 
of study medication 
• 
Section 15 (References): Added reference #20 
for CTCAE version 5  
Version 3.0 
(amendment 2) 
26 Mar 2021 
• 
Study Contacts: Updated email address for 
medical monitor, and added second Covance 
location for Central Laboratory 
• 
Synopsis and Section 4.1: Updated Inclusion 
#10 to exclude herbal supplements only  
• 
Synopsis and Section 4.2: Revised definition 
of uncontrolled hypertension in Exclusion #13 
and added new Exclusion #18 concerning post-
trial treatment 
• 
Sections 5.4, 5.8, and 6:  Added text to clarify 
timing of randomization, which is to occur 
before Day 1, but after confirming eligibility 
and receiving screening testosterone value due 
to just-in-time shipping of study medication 
• 
Table 1: Revised timing of randomization  
• 
Section 5.6.7: Added clarifications around 
other concomitant medication that should be 
used with caution during the study 
• 
Section 5.6.8.2: Added list of notable strong 
CYP3A4 inducers   
• 
Section 5.10: Added text to clarify the 
provision of post-trial treatment, including no 
post-trial access to study medication, and the 
definition of “End of Trial”  
  


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Document Status  
Version Date  
Summary of Key Changes, continued  
Version 3.0 
(amendment 2) 
26 Mar 2021 
• 
Sections 7.1, 7.2.2, 7.2.3, 7.4 and 7.5: 
Added/revised text to better describe timing 
and information needed for reporting AEs, 
SAEs, SUSARs and partner pregnancies 
• 
Section 9.6: Added text to note that additional 
patients may be randomized to ensure that a 
total of 108 patients are treated through Day 9 
for collection of the primary endpoint data 
• 
Section 9.7.1: Clarified the definition of the 
Per Protocol population 
• 
Section 10.3: Added text to explicitly state 
source data should also be readily available 
upon any request from the authorities 
• 
Section 13: Added reference #21 for FDA 
source of strong CYP3A4 inducers 
 
 
 


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Contents 
List of figures ............................................................................................................................ 10 
List of tables ............................................................................................................................. 10 
List of abbreviations ................................................................................................................. 11 
Protocol synopsis ...................................................................................................................... 14 
1 
INTRODUCTION ................................................................................................. 20 
1.1 
Background ............................................................................................................ 20 
1.2 
Investigational medical product ............................................................................. 21 
1.3 
Previous study findings .......................................................................................... 21 
1.3.1 Nonclinical studies ................................................................................................. 21 
1.3.2 Clinical studies ....................................................................................................... 22 
1.3.2.1 Zytiga pharmacokinetics and metabolism ............................................................. 22 
1.3.2.2 Zytiga clinical efficacy and safety ......................................................................... 22 
1.3.2.3 TAVT-45 clinical experience ................................................................................ 23 
1.4 
Clinical rationale .................................................................................................... 25 
1.5 
Purpose ................................................................................................................... 25 
2 
STUDY OBJECTIVES AND ENDPOINTS ......................................................... 26 
2.1 
Primary objective ................................................................................................... 26 
2.2 
Secondary objective ............................................................................................... 26 
2.3 
Endpoints ............................................................................................................... 26 
3 
INVESTIGATIONAL PLAN ................................................................................ 27 
3.1 
Study design ........................................................................................................... 27 
3.2 
Rationale for study design ..................................................................................... 27 
3.3 
Rationale for dose/regimen, route of administration and duration of treatment .... 28 
3.4 
Formulation to be used .......................................................................................... 29 
3.5 
Rationale for choice of additional treatment .......................................................... 30 
3.6 
Purpose and timing of interim analyses/design adaptations .................................. 30 
3.7 
Risks and benefits .................................................................................................. 30 
4 
STUDY POPULATION ........................................................................................ 31 
4.1 
Inclusion Criteria ................................................................................................... 31 
4.2 
Exclusion criteria ................................................................................................... 33 
5 
TREATMENT ....................................................................................................... 34 
5.1 
Study treatment: investigational and control drugs ............................................... 34 
5.2 
Additional treatments ............................................................................................. 34 
5.3 
Treatment arms ...................................................................................................... 35 
5.4 
Treatment assignment and randomization ............................................................. 35 
5.5 
Treatment blinding ................................................................................................. 35 
5.6 
Treating the subject ................................................................................................ 35 
5.6.1 Subject numbering ................................................................................................. 35 


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5.6.2 Dispensing the investigational treatment ............................................................... 35 
5.6.3 Handling of study treatment ................................................................................... 35 
5.6.4 Instructions for prescribing and taking study treatment......................................... 36 
5.6.5 Permitted dose adjustments and interruptions of study treatment ......................... 36 
5.6.6 Rescue medication ................................................................................................. 37 
5.6.7 Concomitant medication ........................................................................................ 37 
5.6.8 Prohibited medication (interaction with other medicinal products and other forms 
of interaction) ......................................................................................................... 37 
5.6.8.1 Abiraterone acetate contraindications .................................................................... 38 
5.6.8.2 Effects of other medicinal products on abiraterone acetate ................................... 38 
5.6.8.3 Effects of abiraterone acetate on other medicinal products ................................... 38 
5.6.9 Discontinuation of study treatment ........................................................................ 38 
5.7 
Withdrawal of consent ........................................................................................... 39 
5.8 
Lost to follow-up.................................................................................................... 39 
5.9 
Emergency breaking of assigned treatment code ................................................... 39 
5.10 
Study completion and post-study treatment ........................................................... 39 
5.11 
Early study termination .......................................................................................... 40 
6 
VISIT SCHEDULE AND ASSESSMENTS ......................................................... 40 
6.1 
Information to be collected on screen failures ....................................................... 43 
6.2 
Subject demographics/other baseline characteristics ............................................. 43 
6.3 
Treatment exposure and compliance ..................................................................... 43 
6.4 
Contraception ......................................................................................................... 43 
6.4.1 
Exposure to Partners During the Study .................................................................. 44 
6.4.2 
Sperm Donation ..................................................................................................... 44 
6.5 
Efficacy assessments .............................................................................................. 44 
6.5.1 
Serum testosterone ................................................................................................. 44 
6.5.2 
Prostate-specific antigen ........................................................................................ 44 
6.5.3 
Abiraterone trough concentrations ......................................................................... 44 
6.6 
Pharmacokinetics ................................................................................................... 45 
6.7 
Safety ..................................................................................................................... 45 
6.7.1 
Clinical laboratory assessments ............................................................................. 45 
6.7.2 
Vital signs .............................................................................................................. 46 
6.7.3 
Electrocardiograms ................................................................................................ 46 
6.7.4 
Physical examination ............................................................................................. 46 
7 
SAFETY MONITORING ...................................................................................... 46 
7.1 
Adverse events ....................................................................................................... 46 
7.2 
Serious adverse events ........................................................................................... 48 
7.2.1 Definition of SAE .................................................................................................. 48 
7.2.2 SAE reporting ........................................................................................................ 49 
7.2.3 Expedited Reporting .............................................................................................. 50 


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7.3 
Adverse Events of Special Interest ........................................................................ 50 
7.4 
Overdose and dosing errors ................................................................................... 50 
7.5 
Pregnancy reporting ............................................................................................... 51 
8 
DATA REVIEW AND DATABASE MANAGEMENT ...................................... 51 
8.1 
Site monitoring ...................................................................................................... 51 
8.2 
Data collection ....................................................................................................... 52 
8.3 
Database management and quality control ............................................................ 52 
8.4 
Data Monitoring Committee .................................................................................. 52 
9 
DATA ANALYSIS ................................................................................................ 53 
9.1 
Study design ........................................................................................................... 53 
9.2 
Efficacy endpoints ................................................................................................. 53 
9.3 
Safety endpoints ..................................................................................................... 53 
9.4 
Pharmacokinetic endpoints .................................................................................... 53 
9.5 
Other endpoints ...................................................................................................... 54 
9.6 
Sample size ............................................................................................................ 54 
9.7 
Data analysis .......................................................................................................... 54 
9.7.1 General analyses .................................................................................................... 54 
9.7.2 Efficacy data analyses ............................................................................................ 55 
9.7.3 Multiplicity and testing strategy ............................................................................ 56 
9.7.4 Safety data analyses ............................................................................................... 56 
9.7.5 Pharmacokinetic data analyses .............................................................................. 56 
9.7.6 Other analyses ........................................................................................................ 56 
10 
ETHICAL CONSIDERATIONS ........................................................................... 57 
10.1 
Regulatory and ethical compliance ........................................................................ 57 
10.2 
Informed consent procedures ................................................................................. 57 
10.3 
Responsibilities of the investigator ........................................................................ 57 
10.4 
Publication of study protocol and results ............................................................... 57 
11 
PROTOCOL ADHERENCE ................................................................................. 57 
12 
PROTOCOL AMENDMENTS ............................................................................. 58 
13 
REFERENCES ...................................................................................................... 59 
 
 
 
 
 


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List of figures 
 
Figure 1                       Study schema .......................................................................................................... 27 
Figure 2                       Structural formula of the study drug (abiraterone acetate) ..................................... 29 
 
 
List of tables 
 
Table 1                      Assessment schedule ................................................................................................ 41 
 
 


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List of abbreviations 
ACTH 
 
Adrenocorticotropic hormone  
ADT 
 
Androgen deprivation therapy 
AE  
 
Adverse Event 
AJCC 
 
American Joint Committee on Cancer  
ALP  
 
Alkaline Phosphatase  
ALT 
 
Alanine Aminotransferase 
ANC 
 
Absolute neutrophil count 
ANOVA 
 
Analysis of variance 
AST  
 
Aspartate Aminotransferase 
AUC 
 
Area under the curve 
AUC0-12 
 
Area under the concentration-time curve from time zero to 12 hours  
AUC0-24 
 
Area under the concentration-time curve from time zero to 24 hours  
AUClast 
Area under the concentration-time curve from time zero to the time of last 
sample with a quantifiable concentration 
BID  
 
Twice daily 
CI  
 
Confidence interval 
Cmax  
 
Maximum plasma drug concentration 
Cmin  
 
Minimum plasma drug concentration 
CRF  
 
Case Report Form  
CR-ITT 
 
Intent-to-treat population for the mCRPC patients 
CRO 
 
Contract Research Organization 
CRPC 
 
Castration-resistant prostate cancer 
CSPC 
 
Castration-sensitive prostate cancer 
CT  
 
Computed tomography 
CTCAE  
 
Common Terminology Criteria for Adverse Events  
DHEA 
 
Dehydroepiandrosterone 
dl 
 
 
Deciliter 
DMC  
 
Data monitoring committee  
ECOG 
 
Eastern Cooperative Oncology Group 
EMA/EMEA 
European Medicines Agency  
ET  
 
Early Termination  
FDA 
 
(U.S.) Food and Drug Administration 
GCP 
 
Good Clinical Practice 
GnRH 
 
Gonadotropin-releasing hormone 


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HbA1c 
 
Hemoglobin A1c 
HBsAg  
 
Hepatitis B surface antigen  
HCV 
 
Hepatitis C virus 
ICF  
 
Informed Consent Form 
ICH 
International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
IEC  
 
Independent Ethics Committee 
IMP  
 
Investigational medicinal products  
IRB  
 
Institutional Review Board 
IRT   
 
Interactive Response Technology 
ITT  
 
Intent-to-treat 
LLOQ 
 
Lower limit of quantification 
LS  
 
Least squares 
mCRPC 
 
Metastatic castration-resistant prostate cancer 
mCSPC 
 
Metastatic castration-sensitive prostate cancer 
MedDRA 
 
Medical dictionary for regulatory activities  
mIU  
 
Milli-International unit 
mm Hg 
            Millimeter of mercury 
MRI  
 
Magnetic resonance imaging 
NCCN 
 
National Comprehensive Cancer Network 
ng  
 
Nanogram 
PFS  
 
Progression-free survival 
PiB  
 
Powder-in-bottle 
PSA  
 
Prostate-specific antigen 
R-AA 
 
Reference abiraterone acetate (Zytiga®) 
Rac  
 
Accumulation index 
RECIST 
 
Response Evaluation Criteria in Solid Tumors 
SAE  
 
Serious Adverse Event 
SE  
 
Standard error 
SmPC 
 
Summary of Product Characteristics 
SUSAR 
 
Suspected unexpected serious adverse reactions 
t½ 
 
 
Effective half-life 
TAVT 
 
Tavanta Therapeutics, Inc. 
TEAE 
 
Treatment-Emergent Adverse Event 
Tmax  
 
Time to maximum plasma concentration 


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TNM  
 
Tumor, node, metastasis system of staging 
ULN 
 
Upper limit of normal 
WHO 
 
World Health Organization 


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Protocol synopsis 
 
 
Name of Sponsor/Company: Tavanta Therapeutics, Inc. (Tavanta) 
Name of Finished Product: TAVT-45 (abiraterone acetate) Granules for Oral Suspension, hereafter 
referred to as TAVT-45 granules 
Name of Active Ingredients: Abiraterone acetate 
Title of Study: 
Phase 3 study investigating the efficacy and safety of TAVT-45 (abiraterone 
acetate) Granules for Oral Suspension (a novel abiraterone acetate formulation) 
relative to a reference abiraterone acetate formulation in patients with 
metastatic Castrate Sensitive Prostate Cancer (mCSPC) and metastatic Castrate 
Resistant Prostate Cancer (mCRPC)  
Principal 
Investigator: 
Multi-center study 
Study Center: 
Multi-center study, including but not limited to, sites in US, Europe and other 
regions 
Development Phase: 
Phase 3 
Primary Objectives: 
To establish therapeutic equivalence between TAVT-45 granules and Zytiga® tablets in patients with 
metastatic castrate sensitive prostate cancer (mCSPC) and metastatic castrate resistant prostate cancer 
(mCRPC)  
Secondary Objective: 
To characterize the multiple-dose pharmacokinetic profile of TAVT-45 in a cohort of patients 
Study Design:  
This is a Phase 3 randomized, open-label study to evaluate the pharmacodynamic effect and safety profile 
of TAVT-45 compared to Zytiga (reference abiraterone acetate formulation, hereafter referred to as R-
AA) in patients with mCSPC and mCRPC. Randomization will be stratified by prostate cancer population 
(CSPC vs CRPC) and baseline testosterone (<10 vs ≥ 10 ng/dL). Patients will be treated for 84 days and 
randomized into one of two groups in a 1:1 ratio: 
• 
TAVT-45:  Administered twice daily as 1 x sachet containing TAVT-45 (250 mg abiraterone 
acetate) + Prednisone (5 mg once or twice daily, depending on prostate cancer population) 
• 
R-AA:  Administered once daily as (2 x 500 mg Zytiga tablets) + Prednisone (5 mg once or 
twice daily, depending on prostate cancer population) 
Methodology: 
At Screening (up to 28 days prior to first dosing), all eligible patients will provide written informed 
consent to participate in the study before any protocol-specified procedures or assessments are initiated.  
Upon meeting all inclusion/exclusion criteria set forth in the protocol, patients will be randomized in a 
1:1 fashion to receive either TAVT-45 (250 mg abiraterone acetate) twice daily (approximately every 12 
hours) without respect to food or R-AA 1000 mg once daily either ≥ 1 hour before or ≥ 2 hours after a 
meal. All patients should also receive prednisone together with a gonadotropin-releasing hormone 
(GnRH) analog concurrently or should have had bilateral orchiectomy. The mCSPC patients will receive 
prednisone 5 mg orally once daily, while the mCRPC patients will receive prednisone 5 mg orally twice 
daily.  Randomization will be stratified by prostate cancer population (CSPC vs CRPC) and baseline 
testosterone (<10 vs ≥ 10 ng/dL).  
Patients will return to the clinic in the morning on Days 9, 10, 28, 56 and 84 for assessments and 
evaluations of safety and efficacy, including testosterone, PSA, and abiraterone trough samples.  Patients 
may return to the clinic or may visit a local laboratory for evaluation of liver function tests on Days 42 
and 70.  Blood samples for testosterone will be taken between the hours of 7:00-10:00 in the morning. A 
pharmacokinetic sub-study will be conducted in a cohort of up to 8 patients receiving TAVT-45 at select 


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site(s) only. Pharmacokinetic profiles over the dosing interval will be obtained on Day 1 (first dose) and 
on Day 9 (steady state).  For all patients, a follow-up phone call will also be made approximately one 
week after the last dose for AE assessments.  
Number of Planned Study Subjects:  
Total patients planned to be enrolled: 108 (n=54 patients per prostate cancer population), randomized in 
a 1:1 ratio receiving either TAVT-45(n=27 mCRPC and n=27 mCSPC patients) or R-AA (n=27 mCRPC 
and n=27 mCSPC patients).  
Inclusion Criteria: 
1. Written informed consent obtained prior to any study-related procedure being performed  
2. Male patients at least 18 years of age or older at time of consent  
3. Pathologically confirmed adenocarcinoma of the prostate  
4. Ongoing therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist (unless 
patient has already had a bilateral orchiectomy) AND serum testosterone level <50 ng/dL at 
screening  
5. Have either metastatic CSPC or metastatic CRPC, as defined below: 
• 
CSPC:   Using the American Joint Committee on Cancer (AJCC) tumor, node, metastasis 
(TNM) system, patients must have Stage Tany Nany M+ (distant metastases) disease AND two 
of the following:  
• Gleason score of 8 or greater 
• Three or more bone scan lesions 
• Measurable visceral metastases 
• 
CRPC: Patients must have metastatic* disease, and must also have disease progression 
according to the recommendations of the Prostate Cancer Working Group 3 by having at 
least one of the following criteria: 
• Two rises of PSA (taken a minimum of 1 week apart) from a baseline measurement 
of at least 1 ng/mL 
• Imaging progression (CT/MRI) by RECIST 1.1 criteria or PET/CT* 
• Nuclear scan progression by 2 or more new bone lesions.  
* Note:  Metastatic disease should be documented by MRI/CT, PET/CT (including, but not 
limited to, standard of care imaging using 18F-fluciclovine, 11C-choline, or PSMA where 
approved) or bone scan. Imaging obtained within 90 days prior to the start of study 
drug/reference product will be accepted. 
6. The following prior treatment and/or surgery for prostate cancer are allowed: 
• 
CSPC:    
• Up to 90 days of androgen deprivation therapy (ADT) with gonadotropin-releasing 
hormone (GnRH) agonists/antagonists or orchiectomy with or without concurrent 
anti-androgens prior to patients’ randomization is permitted 
• Patients may have one course of palliative radiation or surgical therapy to treat 
symptoms resulting from metastatic disease (e.g., impending cord compression or 
obstructive symptoms) if administered prior to randomization 
• Radiation or surgical therapy that was not initiated 4 weeks after the start of ADT or 
orchiectomy 
• 
CRPC: 
• Previous chemotherapy with docetaxel for metastatic disease with treatment 
completed at least 1 year prior to Screening 
7. Discontinuation of flutamide or nilutamide, and other anti-androgens prior to the start of study 
medication; discontinuation of bicalutamide prior to start of study medication.  
8. Discontinuation of strong CYP3A4 inducers at least 4 weeks prior to start of study medication. 


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9. Discontinuation of radiotherapy prior to start of study medication 
10. Discontinuation of herbal supplements at least 4 weeks prior to the first dose of study medication 
and for the duration of the trial.   
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at screening  
12. Normal organ function with acceptable initial laboratory values within the screening period:  
ANC 
≥ 1,500/µl 
Albumin 
Hemoglobin 
> 3.0g/dL 
≥ 9g/dL 
Platelet count 
≥ 100,000/µl 
Serum Creatinine 
≤ 3.0 x the institutional upper limit of normal (ULN) 
Potassium 
> 3.5 mmol/L (within institutional normal range) 
Bilirubin 
≤ 1.5 ULN (unless documented Gilbert's disease) 
SGOT (AST) 
≤ 2.5 x ULN 
SGPT (ALT) 
≤ 2.5 x ULN 
13. Life expectancy of at least 6 months at screening  
14. Patients engaged in sex with women of child-bearing potential agree to use a condom plus another 
effective contraception method.  Patients agree to use a condom when engaged in any sexual activity, 
including sex with a pregnant woman. These restrictions will apply from the time informed consent 
is provided until 3 weeks after the last dose of study medication is taken. 
15.  Patient is willing and able to comply with all protocol requirements assessments  
Exclusion Criteria: 
1. For mCSPC patients: 
• 
Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer not 
specified as allowable treatment in Inclusion Criterion 6. For example, prior therapy with 
apalutamide or enzalutamide is prohibited as well as therapy with an investigational agent 
as described in Exclusion Criterion 16. 
2. For mCRPC patients: 
• 
Prior treatment with abiraterone or enzalutamide is prohibited 
• 
Previous chemotherapy is prohibited with exception of docetaxel treatment as specified in 
Inclusion Criterion 6. 
3. Initiation of bisphosphonate or denosumab therapy within 4 weeks prior to the start of study 
drug/reference product. Patients who are on a stable dose of these medications for at least 4 weeks 
at the time of starting study drug/reference product will be eligible. 
4. Therapy with estrogen within 4 weeks prior to the start of study drug 
5. Use of systemic glucocorticoids equivalent to >10 mg prednisone daily. Patients who have 
discontinued or reduced dosing to the equivalent of ≤ 10 mg prednisone daily within 14 days prior 
to the start of study drug are eligible 
6. Known, symptomatic metastases to the brain or central nervous system involvement (patients with 
asymptomatic and neurologically stable disease for the past 4 weeks will be permitted) 
7. History of adrenal gland dysfunction defined as requiring treatment for adrenal insufficiency  
8. History of other malignancy within the previous 2 years (no longer being actively treated), with the 
exceptions of basal cell carcinoma, non-muscle invasive bladder cancer that has been treated and is 
under surveillance, or other in-situ cancers with a low likelihood of recurrence  
9. Major surgery within 4 weeks prior to the start of study drug 
10. Known gastrointestinal disease or condition that could impair absorption inclusive of gastrocolic 
fistula, gastroenterostomy, biliary obstruction, cirrhosis, chronic pancreatitis or pancreatic cancer, 
cystic fibrosis, amyloidosis, celiac disease, Crohn’s disease, radiation enteritis, intestinal resection, 
and history of bariatric surgery 


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11. Known history of human immunodeficiency virus or seropositive test for hepatitis C virus (HCV) or 
hepatitis B surface antigen (HBsAg) (note: HCV patients with undetectable viral load will be 
eligible) 
12. Poorly controlled diabetes, defined as HbA1c > 8% within the past 12 months  
13. Uncontrolled hypertension at screening 
14. History of New York Heart Association class III or IV heart failure 
15. Serious concurrent illness, including psychiatric illness, that could interfere with study participation 
16. Receipt of another investigational agent within 4 weeks of treatment start or within 5 x the treatment 
half-life, whichever is longer. 
17. Known hypersensitivity or allergy to abiraterone acetate, prednisone or any excipients in the study 
drugs 
18. In the opinion of the investigator, participation in the trial would prevent the patient from receiving 
local standard-of-care treatment for metastatic prostate cancer, if clinically indicated, after 
completion of the trial  
19. Other condition which, in the opinion of the Investigator, would preclude participation in this trial. 
Test Product, Dose and Mode of Administration 
Test product: 
TAVT-45 (250 mg abiraterone acetate) 
Mode of 
administration: 
Oral  
Strength: 
250 mg 
Dose: 
Administered twice daily as 1 x sachet TAVT-45 (250 mg abiraterone 
acetate) reconstituted in either water or juice, as specified in the medication 
preparation guide 
Reference Product, Dose and Mode of Administration 
Reference product: 
Reference abiraterone acetate (R-AA; Zytiga tablets) 
Mode of 
administration: 
Oral 
Strength: 
500 mg Zytiga tablets 
Dose: 
Administered once daily as 2 x 500 mg Zytiga tablets, swallowed whole with 
water 
Additional Product, Dose and Mode of Administration 
Additional product: 
Prednisone 
Mode of 
administration: 
Oral 
Strength: 
5 mg tablets 
Dose: 
mCRPC Patients: 5 mg twice daily 
mCSPC Patients: 5 mg once daily 
Duration of Treatment: 
For an individual patient, the duration of the clinical study will be up to approximately 17 weeks 
(including a Screening Phase up to 28 days, an 84-day treatment period, and a 1-week follow up period).  
Efficacy Assessments: 
Efficacy assessments will include: 
• 
Serum testosterone 
• 
Prostate specific antigen (PSA) 
• 
Trough concentrations of abiraterone 


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Pharmacokinetic Assessments: 
In a cohort of up to 8 patients randomized to TAVT-45, blood samples (approximately 4 mL each) for 
PK analysis will be collected at the following times on Day 1 and Day 9: pre-dose (time 0) and  0.25, 
0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 10, and 12 hours post-dose and before the scheduled evening dose.   
Safety Assessments: 
Safety assessments will include: 
• 
Vital signs 
• 
Physical examinations 
• 
Adverse events (AEs) 
• 
Clinical laboratory assessments 
Criteria for Evaluation:  
Efficacy: 
The primary efficacy endpoint is the comparison of the average of serum testosterone levels on days 9 
and 10 between groups (TAVT-45 vs R-AA). 
The key secondary efficacy endpoint is the PSA-50 response, defined as a decrease of ≥ 50% in PSA 
levels from baseline at any time over the 84-day post-treatment period. 
Other secondary efficacy endpoints are as follows:  
• 
Serum testosterone levels at Days 28, 56 and 84 
• 
PSA-50 response at Days 28, 56 and 84 
• 
PSA levels at Days 28, 56 and 84 
• 
Trough concentrations of abiraterone at Days 9, 28, 56 and 84 
 
Safety:  Safety endpoints include incidence of treatment emergent adverse events (TEAE), and clinically 
relevant changes in vital signs and laboratory assessments. 
 
Pharmacokinetics:  For a cohort of up to 8 patients randomized to TAVT-45 and participating in the 
serial PK sampling on Day 1 and Day 9, the following PK parameters will be determined: 
• 
Area under the concentration-time curve from time zero to 12 hours post dose (AUC0-12)  
• 
Maximum measured plasma concentration (Cmax)  
• 
Minimum measured plasma concentration (Cmin)  
• 
Time to maximum measured concentration (tmax)  
• 
Accumulation ratio (Rac) 
• 
Effective half-life (t½) 
Statistical Methods: The effects of TAVT-45 250 mg BID on serum testosterone will be compared to 
R-AA (1000 mg QD) based on the equivalence approach of 80% to 125% confidence interval (CI) of the 
test-to-reference geometric mean ratio. Under the assumptions of a coefficient of variation of 25%, a 
lower and upper limit of 80% to 125%, and an expected test-to-reference ratio of 1.05, 108 patients in 
total (54 patients in TAVT-45 and 54 patients in R-AA) will provide over 80% power (two one-sided t-
tests at 0.05 level) to conclude therapeutic equivalence of TAVT-45 to R-AA. 
The primary endpoint, the average serum testosterone levels on days 9 and 10, will be analyzed by an 
analysis of variance (ANOVA) model with treatment as a factor. The test-to-reference geometric mean 
ratio effect and its 90% confidence interval (CI) of TAVT-45 to R-AA will be compared to 80% to 125% 
limit [1,2] . The primary analysis will be performed on the mCRPC intent-to-treat (CR-ITT) population 
and repeated on the ITT and per-protocol populations. Primary analysis will also be repeated on CSPC 
patients. Different missing data imputation approaches will be used as sensitivity analyses based on the 
intent-to-treat population. If the equivalence of the average of serum testosterone levels on days 9 and 
10 is achieved, then the key secondary endpoint (PSA-50 response) will be tested at 0.05 alpha level. 


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Safety will be assessed in all patients who received at least one dose of study drug. Treatment-emergent 
AEs, along with the number and percentage of patients with abnormal or potentially clinically significant 
clinical laboratory values and vital sign measurements, will be summarized by treatment. Hypothesis 
testing, unless otherwise indicated, will be performed at the 5% significance level. 


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1 
INTRODUCTION 
1.1 
Background 
Abiraterone acetate is rapidly converted in vivo to abiraterone, a selective, irreversible inhibitor 
of cytochrome P450 17α (17α-hydroxylase/C17-20 lyase; CYP17), an enzyme that is key in the 
production of androgens in all sites, including the testes and adrenal glands. CYP17 catalyses the 
conversion 
of 
pregnenolone 
and 
progesterone 
into 
testosterone 
precursors, 
dehydroepiandrosterone (DHEA) and androstenedione [3,4]. Inhibition of this biochemical 
process results in decreased proliferation of androgen sensitive castration-resistant prostate cancer 
(CRPC) cell lines and slower disease progression in patients. 
Abiraterone acetate is indicated for the treatment of metastatic castration-resistant prostate cancer 
(mCRPC) and metastatic high-risk castration-sensitive prostate cancer (CSPC), in combination 
with prednisone in the US and in combination with either prednisone or prednisolone in Europe. 
Abiraterone acetate is currently marketed under the trade name Zytiga as film-coated tablets 
containing 500 mg abiraterone acetate and as uncoated tablets containing 250 mg. The 
recommended 
dose 
for 
Zytiga 
is 
1000 
mg 
orally 
once 
daily, 
together 
with 
prednisone/prednisolone (5 mg orally twice daily for mCRPC patients; and 5 mg orally once daily 
for high-risk CSPC patients). Patients receiving Zytiga should also receive a gonadotropin-
releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy [3,4]. 
Abiraterone acetate has been shown to be safe and effective in both the CRPC and high-risk CSPC 
populations with distant metastases (M1, according to the American Joint Committee on Cancer 
[AJCC] tumor, node, metastasis [TMN] system). Of note, abiraterone acetate is also recommended 
as Category 1 evidence by the National Comprehensive Cancer Network (NCCN) as first-line 
treatments for both populations (i.e., nodal metastases [N+M0]). 
Administration of Zytiga with food, compared with administration in a fasted state, results in up 
to a 10-fold (AUC) and up to a 17-fold (Cmax) increase in mean systemic exposure of abiraterone, 
depending on the fat content of the meal. Given the normal variation in the content and 
composition of meals, taking Zytiga with meals has the potential to result in highly variable 
exposures. Therefore, Zytiga must not be taken with food. It should be taken at least two hours 
after eating and no food should be eaten for at least one hour after taking Zytiga. The 10-fold food 
effect observed also shows that the oral bioavailability of abiraterone is below 10% when Zytiga 
is administered in the fasted state. Inter-subject variability has been shown to be approximately 
79% for Cmax and 64% for AUC0-24 after multiple day dosing. 
The objective of the TAVT-45 development program was to develop an abiraterone acetate 
formulation with improved oral bioavailability through enhanced solubility in the fasted state, 
thereby decreasing the food effect observed after the oral administration of Zytiga. This would 
eliminate the requirement of taking the drug on an empty stomach, would allow significant 
reduction of the dose, and would reduce the high variability of exposure. Additionally, and 
importantly, the oral suspension formulation of TAVT-45 addresses the unmet medical need of 
prostate cancer patients who have difficulty swallowing the currently approved 500 mg filmcoated 
tablet and the 250 mg uncoated tablet formulations of Zytiga. Both presentations require patients 
to swallow multiple, large tablets daily. This is of particular importance since dysphagia, defined 
as difficulty or discomfort in swallowing, has been reported to affect ~20% to 40% of cancer 
patients and can impact compliance to prescribed medications due to difficulty swallowing pills 
[5,6,7]. As an oral suspension, TAVT-45 provides an alternative formulation and choice for cancer 
patients with and without dysphagia and reduces the pill burden in these patients. 


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1.2 
Investigational medical product 
The following investigational medicinal products (IMPs) will be used in this clinical study: 
   
• 
TAVT-45:  Administered twice daily as 1 x sachet containing TAVT-45 (250 mg 
abiraterone acetate).  Each sachet is reconstituted in water or specified fruit juice. 
• Reference abiraterone acetate (R-AA):  Administered once daily as (2 x 500 mg Zytiga 
tablets).  Tablets are administered with water.  
1.3 
Previous study findings 
Three novel formulations of abiraterone acetate have been used to support the clinical 
development.  Initial formulations were identified as DRGT-45, while the final formulation to be 
evaluated in this study is identified as TAVT-45.  
Initially, a powder-in-bottle (PiB) formulation with 50 mg abiraterone acetate per bottle strength 
was developed and tested in both non-clinical studies and a Phase 1 clinical trial. Since the 
production of the PiB formulation at industrial scale is not viable and PiBs are generally not 
preferred as final marketed dosage forms, DRGT-45 tablets for oral suspension (with 62.5 mg 
strength) were developed.  The DRGT-45 tablets for oral suspension were used in one Phase 1 
clinical trial and whilst the clinical data was acceptable, the tablets were found to have a high level 
of friability which could impact on the physical integrity of the tablets when manufactured at large 
scale or distributed for use outside of a controlled clinical setting. To address the tablet friability 
issue, the tablet manufacturing process was modified to deliver a granule form (TAVT-45) which 
had an identical formulation composition but was a granule in place of a tablet. The granules are 
packaged in a sachet as the primary packaging which is composed of the same material used in 
primary packaging of the tablets. Characterization studies were performed to confirm that the 
reconstitution properties (time and reconstitution method) of the granules were comparable to that 
of the tablets and also that the properties of the reconstituted granules in water and fruit juice were 
equivalent in terms of homogeneity and stability compared to that obtained when reconstituting 
the tablets in water.  The granule formulation of TAVT-45 will be used in this study. 
1.3.1 
Nonclinical studies 
The non-clinical aspects of abiraterone acetate are well documented [3,4]. Bridging studies, 
however, using DRGT-45 PiB, DRGT-45 tablet for oral suspension, and TAVT-45 granules for 
oral suspension have been undertaken.  Comparisons of DRGT-45 PiB and DRGT-45 tablet for 
oral suspension have been assessed in vitro and in vivo and TAVT-45 granules have been assessed 
in vitro. The aim of the non-clinical investigation was to assess the pharmacokinetic properties of 
the novel formulations using in vitro dissolution and permeability measurements along with in 
vivo pharmacokinetic investigations in beagle dogs for the DRGT-45 tablet for oral suspension.  
Since the formulation composition of the DRGT-45 tablet and TAVT-45 granules are the same 
and the in vitro dissolution and properties of the reconstituted products are comparable, the in 
vivo pharmacokinetic investigation in vivo has not been repeated for the TAVT-45 granules. 
Full details of nonclinical assessments may be found in the TAVT-45 Investigator Brochure 
[8]. 


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1.3.2 
Clinical studies 
Abiraterone acetate has been investigated extensively as Zytiga in healthy volunteers and patients 
[3, 4]; further clinical study results are available in the Investigator’s Brochure [8], and are 
discussed below.  
There has been one clinical study conducted with the DRGT-45 PiB formulation, and one clinical 
study with this DRGT-45 tablet for oral suspension formulation, which are both briefly discussed 
below in Section 1.3.2.3.  
1.3.2.1 
Zytiga pharmacokinetics and metabolism  
Following administration of Zytiga, the PK of abiraterone and abiraterone acetate have been 
studied in healthy subjects, patients with metastatic advanced prostate cancer and subjects without 
cancer with hepatic or renal impairment. Abiraterone acetate is rapidly converted in vivo to 
abiraterone, an androgen biosynthesis inhibitor.  
Following oral administration of abiraterone acetate in the fasting state, the time to reach 
maximum plasma abiraterone concentration is approximately 2 hours. No major deviation from 
dose proportionality was observed in the dose range of 250 to 1000 mg. Steady state is achieved 
within eight days following once-daily dosing of 1000 mg, with approximately 2-fold higher 
exposure at steady state (steady state AUC) compared to when the same dose is administered as a 
single dose. Inter-subject variability has been shown to be approximately 79% for Cmax and 64% 
for AUC0-24 after multiple day dosing. 
Following oral administration of 14C-abiraterone acetate as capsules, abiraterone acetate is 
hydrolysed to abiraterone, which then undergoes metabolism including sulphation, hydroxylation 
and oxidation primarily in the liver. The majority of circulating radioactivity (approximately 92%) 
is found in the form of metabolites of abiraterone. Approximately 88% of the radioactive dose is 
recovered in faeces and approximately 5% in urine. 
Administration of abiraterone acetate with food, compared with administration in a fasted state, 
results in up to a 10-fold (AUC) and up to a 17-fold (Cmax) increase in mean systemic exposure of 
abiraterone, depending on the fat content of the meal. Given the normal variation in the content 
and composition of meals, taking Zytiga with meals has the potential to result in highly variable 
exposures. The mean half-life of abiraterone in plasma is approximately 15 h based on data from 
healthy subjects. 
The plasma protein binding of 14C-abiraterone in human plasma is 99.8%. The apparent volume 
of distribution is approximately 5630 L suggesting that abiraterone extensively distributes to 
peripheral tissues [4]. 
1.3.2.2 
Zytiga clinical efficacy and safety 
Zytiga decreases serum testosterone and other androgens to levels lower than those achieved by 
the use of gonadotropin-releasing hormone (GnRH) analogues alone or by orchiectomy. This 
results from the selective inhibition of the CYP17 enzyme required for androgen biosynthesis. 
The key studies with Zytiga include two randomized placebo-controlled, multicenter Phase 3 trials 
in patients with metastatic CRPC (COU-AA-301 and COU-AA-302) and one randomized 
placebo-controlled, multicenter Phase 3 trial (LATITUDE) in patients who had metastatic high-
risk CSPC [9,10,11]. In these trials, Zytiga was administered orally at a dose of 1,000 mg daily in 
combination with prednisone 5 mg (twice daily for mCRPC patients and once daily for high-risk 
CSPC), and added to standard androgen deprivation therapy (ADT), consisting of either a 
gonadotropin-releasing hormone (GnRH) analog or prior orchiectomy.  In the mCRPC patients, 


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overall survival was prolonged in the Zytiga–prednisone group compared to the placebo–
prednisone group in both patients who previously received chemotherapy [9] and those who were 
chemotherapy naïve [10]. Similarly, in patients with metastatic high-risk CSPC, addition of 
Zytiga-prednisone to ADT significantly increased overall survival and radiographic progression-
free survival in men with newly diagnosed, metastatic, CSPC [11]. These studies also 
demonstrated that Zytiga was well tolerated. Most toxic effects were predominantly grade 1 or 2, 
with a low rate of drug discontinuation or dose reduction and were largely mechanism-based and 
secondary to mineralocorticoid excess resulting from blockade of CYP17. The common adverse 
events (≥1%) resulting in discontinuation of Zytiga-prednisone were hepatotoxicity and cardiac 
disorder.  
The current NCCN guidelines for treatment of prostate cancer also recommends Zytiga usage in 
high-risk CSPC patients with nodal metastases (N+ M0). This is based, in part, on the findings 
from the STAMPEDE trial, which demonstrated that adding abiraterone leads to an increased life 
expectancy and improvement in disease control in newly diagnosed metastatic or node-positive 
disease [12]. 
An additional observational study showed that abiraterone trough concentration correlates with 
PSA response and progression-free survival (PFS). Moreover, a cut-off value for plasmatic 
concentration (8.4 ng/mL) was determined for PSA response [13]. These data show that there is a 
relationship between steady state abiraterone trough concentrations, primary treatment resistance, 
and efficacy response (PSA and PFS). Of note, since Zytiga exhibits highly variable PK, low 
plasma abiraterone concentrations are not infrequent. This highlights a major limitation for Zytiga. 
1.3.2.3 
TAVT-45 clinical experience 
Tavanta initially performed one clinical study in healthy male volunteers using an initial 
DRGT-45 PiB formulation. Study DRGT45C01 was a single center, open-label, non-randomized, 
single dose, fixed sequence, 2-way crossover study in 11 healthy male subjects, whereby 
DRGT-45 PiB was dosed at 100 mg and 200 mg doses in the fasted state and at 200 mg dose in 
the fed state, with a minimum washout period between doses of 7 days.  Following the 
administration of DRGT-45 PiB, the mean abiraterone plasma concentrations increased rapidly to 
peak and declined in a biphasic manner. Mean Tmax occurred within 1 hour regardless of the dose 
or prandial status. For the 200 mg dose, abiraterone was detectable in plasma for up to 72 hours 
(> 0.2 ng/ml), while for the 100 mg dose it was detectable for up to 48 hours. The calculated PK 
parameters were compared to literature data available across multiple studies for 1,000 mg Zytiga 
[14]. Following the administration of 100 mg PiB in the fasted state, Cmax and AUC were 88% 
and 33% of that following the administration of 1,000 mg Zytiga, respectively. At the 200 mg 
dose in the fasted state, Cmax exceeded that of 1,000 mg Zytiga by over 2-fold, while AUC was 
81% of the 1,000 mg Zytiga. Increasing the dose from 100 mg to 200 mg resulted in a 2.5-fold 
increase in AUC. Inter-subject variability (expressed as CV%) was also reduced from 59% 
(Zytiga) to 38% (100 mg dose) and 29% (200 mg dose). Food slightly delayed absorption and 
reduced the AUC by 26%. The terminal elimination half-life was similar to that reported for 
Zytiga [3, 14]. There were no serious adverse events (SAEs) or deaths reported during this study. 
All AEs were assessed as mild and unrelated to study drug. The most common TEAEs reported 
by at least 2 subjects were musculoskeletal pain (back/joints) and headache. Other TEAEs 
reported were nasopharyngitis, blood creatine phosphokinase and transaminase increase. There 
were no other clinically significant changes reported in hematological, clinical chemistry or 
urinalysis laboratory values, vital signs measurements, physical examinations, or 12-lead ECGs. 
Tavanta then performed one clinical study in healthy male volunteers using the DRGT-45 tablet 
for oral suspension formulation. Study DRGT45C03 was a single center, randomized crossover 


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trial to evaluate the PK and safety of single doses of DRGT-45 tablets for oral suspension (Part 1; 
doses of 62.5 to 250 mg in 12 healthy adult males) and to compare the oral bioavailability of 
DRGT-45 (250 mg) and R-AA (1000 mg) under fed and modified fasting conditions (Part 2; in 
20 healthy adult males).  
Part 1:  Following single oral administration of DRGT-45 at doses of 62.5, 125, 187.5 and 250 mg, 
abiraterone was rapidly absorbed with median Tmax occurring between 0.50 h and 1.50 h post-
dose across the 62.5 to 250 mg dose range. Exposure to abiraterone increased in a dose supra-
proportional manner. A doubling of the dose of DRGT-45 would result in a 3.11-fold, 3.14-fold 
and 3.05-fold average increase in exposure as measured by Cmax, AUC0-last, and AUC0-∞, 
respectively. The geometric mean plasma half-life of abiraterone was 10.379 h for the 62.5 mg 
dose level and increased to range from 14.045 to 15.038 h at the 125, 187.5 and 250 mg dose 
levels which was similar to those observed previously, and likely the result of better definition of 
the terminal portion of the curve at higher doses (median Tlast increased from 24 h at the 62.5 mg 
dose level to 71 h at the 187.5 and 250 mg dose levels).  
Single oral doses of DRGT-45 up to 250 mg in the fasted state were well tolerated and there were 
no deaths during the study. Six (50.0%) subjects reported a total of 14 AEs after dosing with 
DRGT-45 in Part 1. The overall incidence of AEs was low across all dose levels and the majority 
of AEs were mild in severity and unrelated to DRGT-45. Two subjects were withdrawn due to 
AEs during Part 1 of the study. One subject had an unrelated SAE that that was of moderate 
severity and led to withdrawal from the study (buttock abscess). One subject was withdrawn due 
to maculopapular rash that was mild in severity and considered possibly related to DRGT-45. 
There were no significant clinical laboratory, vital signs or ECG results. 
 
Part 2: Administration of DRGT-45 at 250 mg with a high-fat breakfast showed a statistically 
significant reduction of 59.61%, 24.88% and 24.74% in Cmax, AUC0-last and AUC0-∞ of 
abiraterone, respectively, compared to the fasted state. Median Tmax was unchanged in the fed 
state compared with the fasted state at 0.500 hours and this was confirmed by the statistical 
analysis. The parameters associated with exposure of abiraterone in the fasted treatment group in 
Part 2 were consistent with same treatment in Part 1. Elimination of abiraterone was unchanged 
in the fed state, with geometric mean terminal half-life of 14.624 hours, and was also similar to 
that seen in the fasted state in Part 1.  
Administration of R-AA at 1000 mg 2 hours after a high-fat breakfast (modified fasting 
conditions) showed a delay of 1.5 hours in median Tmax to 3.000 hours compared with the same 
dose in the fasted state. This delay is likely due to delayed gastric emptying in the fed state, and 
median Tmax in both fasted and modified fasted states was later than that of DRGT-45. The Cmax, 
AUC0-last and AUC0-∞ values were 782%, 650% and 642% higher in the modified fasted state than 
the fasted state. Elimination of abiraterone was similar in the fed state to the fasted state, with 
geometric mean terminal half-life of 13.829 hours. 
Following administration of 250 mg DRGT-45 in the fed state, exposure was approximately 
equivalent to or moderately higher than that of 1000 mg R-AA in the fasted state, with Cmax 
bioavailability of 121.11% and AUC0-last and AUC0-∞ bioavailability of 91.24% and 90.46%, 
respectively. Conversely, when compared to that of 1000 mg R-AA dosed in the modified fasted 
state, representing an upper safety limit for the exposure range, exposure levels were notably less 
than the reference regimen (relative bioavailabilities of 15.47%, 14.00% and 14.10% for Cmax, 
AUC0-last and AUC0-∞, respectively) indicating that fed dosing did not represent any exposure 
driven safety concerns.  
Although administration of DRGT-45 at 250 mg with a high-fat breakfast showed a statistically 
significant reduction in abiraterone exposure levels compared to fasted dosing, similar 


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conclusions can be drawn for 250 mg DRGT-45 dosed in the fasted state when comparing to the 
reference Zytiga regimens. Comparisons to 1000 mg R-AA in the fasted state indicated increased 
abiraterone exposure for the DRGT-45 regimen with relative bioavailabilities of 299.83%, 
121.46% and 120.19% for Cmax, AUC0-last and AUC0-∞, respectively. In spite of the negative food 
effect, abiraterone exposure levels following fasted DRGT-45 dosing (relative bioavailabilities of 
59.61%, 24.88% and 24.74% for Cmax, AUC0-last and AUC0-∞, respectively, when compared with 
fed dosing) were also notably less than that observed for R-AA dosed in the modified fasted state. 
The notable gap that exists between DRGT exposure, regardless of prandial state dosed, and the 
upper end of Zytiga exposure, highlights there exists a wide safety related exposure margin for 
future increases in DRGT-45 dose or modification in dose regimens (e.g., BID dosing). 
Additionally, DRGT-45 dosing was associated with lower variability than for R-AA, regardless 
of prandial status (CV% for Cmax was 48.0-60.4% vs 58.6-72.3%, respectively; and CV% for 
AUC0-∞ was 44.0-45.1% vs 55-56.3%). 
Single oral doses of 250 mg DRGT-45 and 1000 mg R-AA administered in the fed and fasted 
state were well tolerated in healthy male subjects and the incidence and nature of AEs was similar 
after dosing with DRGT-45 and R-AA. The incidence of AEs was low across all dosing regimens 
and the majority of AEs were both mild in severity and unrelated to IMP. Twelve (60.0%) subjects 
reported 22 AEs after dosing with DRGT-45 and R-AA. There were no deaths, severe AEs, SAEs 
or AEs leading to withdrawal during Part 2 of the study and there were no significant clinical 
laboratory, vital signs or ECG results. 
1.4 
Clinical rationale 
The low bioavailability, significant food effect and the highly variable nature of abiraterone PK 
after dosing with Zytiga results in known efficacy and potential safety issues. As noted above, it 
has been shown that patients who exhibited primary resistance to 1,000 mg Zytiga had lower 
plasma abiraterone concentrations when compared to responders [13]. Therefore, TAVT-45 is 
being developed to have an abiraterone acetate formulation with improved oral bioavailability, 
and thus the highly variable nature of abiraterone exposure seen after Zytiga dosing is expected 
to be reduced with TAVT-45 dosing. This may result in a greater proportion of patients having 
abiraterone trough concentrations exceeding the 8.4 ng/mL threshold after TAVT-45 treatment 
compared to Zytiga. Moreover, through enhanced solubility in the fasted state, it is expected that 
TAVT-45 would decrease the positive food effect observed after the oral administration of Zytiga, 
eliminating the requirement of taking the drug on an empty stomach. The improved bioavailability 
of TAVT-45 would also allow significant reduction of the dose compared to Zytiga. Finally, 
TAVT-45 would be the first and only anti-androgen therapy that does not increase patient pill-
burden in that it is dosed as a suspension in water or fruit juice. The oral suspension formulation 
of TAVT-45 also addresses the unmet medical need of prostate cancer patients who have difficulty 
swallowing the currently approved 500 mg film-coated tablet and the 250 mg uncoated tablet 
formulations of Zytiga. This is of particular importance since dysphagia, defined as difficulty or 
discomfort in swallowing, has been reported to affect ~20% to 40% of cancer patients and can 
impact compliance to prescribed medications due to difficulty swallowing pills [5,6,7].  
1.5 
Purpose 
This study aims to establish therapeutic equivalence of clinical efficacy and safety between 
TAVT-45 and Zytiga in patients with mCSPC (distant metastases) and mCRPC.  


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2 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
Primary objective 
The primary objective of this study is to establish therapeutic equivalence between TAVT-45 
granules and Zytiga tablets, hereafter referred to as reference abiraterone acetate (R-AA), in 
patients with mCSPC and mCRPC. 
2.2 
Secondary objective 
The secondary objective of this study is to characterize the multiple-dose pharmacokinetic profile 
of TAVT-45 in a cohort of patients. 
2.3 
Endpoints 
Efficacy: 
The primary efficacy endpoint is the comparison of the average of serum testosterone levels on 
days 9 and 10 between groups (TAVT-45 vs R-AA).  
The key secondary efficacy endpoint is the PSA-50 response, defined as a decrease of ≥ 50% in 
PSA levels from baseline at any time over the 84-day post-treatment period. 
Other secondary efficacy endpoints are as follows: 
• Serum testosterone levels at Days 28, 56 and 84 
• PSA-50 response at Days 28, 56 and 84 
• PSA levels at Days 28, 56 and 84 
• Trough concentrations of abiraterone at Days 9, 28, 56 and 84 
Safety:   
Safety endpoints include incidence of treatment emergent adverse events (TEAE), and clinically 
relevant changes in vital signs and laboratory assessments. 
For more details on study endpoints, see Section 9. 
Pharmacokinetics: 
For a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK 
sampling on Day 1 and Day 9, the following PK parameters will be determined: 
• Area under the concentration-time curve from time zero to 12 hours post dose (AUC0-12)  
• Maximum measured plasma concentration (Cmax)  
• Minimum measured plasma concentration (Cmin)  
• Time to maximum measured concentration (tmax)  
• Accumulation ratio (Rac) 
• Effective half-life (t½) 
 


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3 
INVESTIGATIONAL PLAN 
3.1 
Study design 
This is a Phase 3 randomized, open-label study to evaluate the pharmacodynamic effect of TAVT-
45 compared to Zytiga (reference abiraterone acetate formulation, hereafter referred to as R-AA) 
in patients with mCSPC (distant metastases) and mCRPC. Randomization will be stratified by 
prostate cancer population (CSPC vs CRPC) and baseline testosterone (< 10 vs ≥ 10 ng/dL).  
Patients will be treated for 84 days and randomized into one of two groups in a 1:1 ratio: 
• TAVT-45:  Administered twice daily as 1 x sachet TAVT-45(250 mg abiraterone acetate) 
+ Prednisone (5 mg once or twice daily, depending on prostate cancer population) 
• R-AA: Administered once daily as 2 x 500 mg Zytiga tablets + Prednisone (5 mg once or 
twice daily, depending on prostate cancer population) 
 
 
Figure 1                       Study schema  
 
 
 
It is planned to enroll 108 patients in this study (n=54 patients per prostate cancer population), 
randomized in a 1:1 ratio receiving either TAVT-45 (n=27 mCRPC and n=27 mCSPC patients) 
or R-AA (n=27 mCRPC and n=27 mCSPC patients). 
3.2 
Rationale for study design 
Because this study will administer TAVT-45 at 250 mg BID, while maintaining the standard 
approved dosing of once daily R-AA (i.e., 1000 mg QD), as discussed below, it is not possible to 
directly compare the PK profile between these two agents using a traditional bioequivalence of 
Cmax and AUC.  Therefore, this study aims to establish therapeutic equivalence of clinical efficacy 
and safety.  
This study will evaluate serum testosterone levels after treatment with TAVT-45 compared to 
R-AA as the primary efficacy endpoint to show equivalent pharmacodynamic effects. 
Testosterone suppression has been recognized by the FDA as an appropriate efficacy endpoint for 
establishing efficacy of GnRH agonists and antagonists that are approved after the 


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originator/prototype agents. Using serum testosterone as the primary endpoint for clinical 
equivalence is also consistent with the study design used in the STAAR study, which was a 
randomized phase 2 therapeutic equivalence study of abiraterone acetate fine particle formulation 
(Yonsa®) vs. originator abiraterone acetate (Zytiga) in patients with mCRPC [15]. Like the 
STAAR study, this study will also assess serum testosterone on Days 9 and 10 of treatment, which 
aligns with the expected attainment of steady state abiraterone plasma concentrations. The safety 
and tolerability profiles will also be examined, together with other measures of efficacy, including 
PSA, which is the key secondary efficacy endpoint that will provide further supportive evidence 
of the clinical similarity between TAVT-45 and R-AA. 
The two study populations, mCRPC and mCSPC, will be randomized in a 1:1 ratio to ensure 
balance of the populations across the two treatment groups.  Likewise, randomization will be 
stratified by baseline testosterone levels (< 10 and ≥ 10 ng/dL) to ensure balance in each treatment 
arm.  The testosterone stratification threshold of 10 ng/dL was selected considering the baseline 
levels reported in the STAAR study for the patients with mCRPC [15] as well as average 
testosterone values observed following bilateral orchiectomy [16]. 
3.3 
Rationale for dose/regimen, route of administration and duration of 
treatment 
The dose level of R-AA for this study is 1000 mg once daily, which is the standard approved dose 
level [3].  
The dose level of TAVT-45 will be 250 mg BID, which corresponds to a total daily dose of 
500 mg. Selection of this dosing regimen is supported by single dose data from the Phase 1 PK 
study DRGT45C03 (see also Section 1.3.2.3 for details). One of the aims of Part 2 of this study 
was to have an in-study comparison between DRGT-45 and R-AA for PK bioequivalence 
assessments after single doses. Of specific interest was to evaluate whether abiraterone exposure 
after 250 mg DRGT-45 dosing was at least PK bioequivalent or higher than the lower limit (i.e, 
1000 mg R-AA under fasted conditions) and at most PK bioequivalent or lower than the upper 
limit (i.e., 1000 mg R-AA under modified fasted conditions). Key findings are summarized below: 
• Lower Limit: Following administration of 250 mg DRGT-45 in the fed state, peak 
exposure (Cmax) was approximately equivalent to or moderately higher than that of 
1000 mg R-AA in the fasted state, while overall exposure (AUC0-last and AUC0-∞) was 
approximately equivalent to or moderately lower. Similar findings were observed 
following 250 mg DRGT-45 in the fasted state, whereby peak exposure was greater than 
that of 1000 mg R-AA in the fasted state and overall exposure was equivalent to or greater. 
• Upper Limit: When compared to that of 1000 mg R-AA dosed in the modified fasted state, 
representing an upper safety limit for the exposure range, both peak and overall exposure 
levels after DRGT-45 dosing were notably less than the reference regimen (relative 
bioavailabilities for Cmax and AUC ranged from approximately 14-38%). The gap that 
exists between DRGT-45 exposure, regardless of prandial state dosed, and the upper end 
of Zytiga exposure, highlights that there is a wide safety-related exposure margin for future 
increases in DRGT-45 dose or modification in dose regimens (e.g., BID dosing). 
• Simulations of BID Dosing: Simulation of repeated dosing was also performed based on 
the single dose PK data. The predicted plasma concentrations and exposures after dosing 
with DRGT-45 250 mg BID fell within the range observed for R-AA 1000 mg QD at 
steady-state. Based on low trough concentrations at 12-hours post-dose, Cmax is predicted 
to be only slightly increased in steady state (5-10%) for DRGT-45 250 mg BID. 


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In the study described herein, R-AA will be administered orally either ≥ 1 hour before or ≥ 2 hours 
after a meal.  TAVT-45 will be administered without respect to food with the exception of dose 
administration in the pharmacokinetic sub-study.  Patients participating in the serial blood draws 
on Days 1 and 9 will administer TAVT-45 in the fasted state (minimum of 8 h fast) on these days 
and may resume normal meal schedules 2 h after administration of the TAVT-45. 
The duration of treatment in this study will be 84 days (12 weeks). This is equivalent to three 
28-day cycles, and consistent with the STAAR study that also compared a novel abiraterone 
formulation to R-AA [15]. Moreover, 12 weeks is a time point that is historically used in many 
metastatic CRPC studies as a landmark for measuring response to therapy; for example, PSA 
responses at 12 weeks was a statistically significant factor associated with survival in a 
multivariate analysis using a prognostic model applied to multiple clinical trials [17,18].  
For the dose selection and timing of the concomitant prednisone, see Section 3.5.  
3.4 
 Formulation to be used 
This study will use TAVT-45 and R-AA (which is the reference abiraterone acetate currently 
marketed under the trade name Zytiga). 
Abiraterone acetate is the acetyl ester of abiraterone, which is an inhibitor of CYP17. The 
chemical designation is 3β-acetoxy-17-(3-pyridyl)-androsta-5,16-diene.  It is a white to off-white 
powder practically insoluble in aqueous media (pH range 2.0 to 12.9), very slightly soluble in 
0.1N HCl solution and soluble to freely soluble in organic solvents. Abiraterone acetate is 
classified as Class IV compound (low solubility low permeability) according to the 
biopharmaceutical classification system (BCS). Its empirical formula is C26H33NO2. The 
structural formula is shown in Figure 2. 
 
Figure 2                       Structural formula of the study drug (abiraterone acetate) 
 
 
R-AA tablets are available as film-coated tablets containing 500 mg abiraterone acetate and as 
uncoated tablets containing 250 mg. The excipients used in the formulation of Zytiga are lactose 
monohydrate, microcrystalline cellulose, croscarmellose sodium, povidone, sodium lauryl sulfate, 
magnesium stearate and colloidal silicon dioxide.  
TAVT-45 granules contain 3.83% abiraterone acetate as active ingredient along with 19.13% 
Plasdone K12, 0.03% BHT and 0.03% BHA, 15.31% Soluplus, 0.50% Aerosil 200, 2.30% 
Sodium deoxycholate, 23.27% Microcrystalline cellulose, 21.36% Lactose/Lactose monohydrate, 
11.63% Crospovidone, 2.00% PEG4000, 0.43% Sodium stearyl fumarate and 0.20% Saccharin 
Sodium as excipients.  


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3.5 
Rationale for choice of additional treatment 
In addition to the TAVT-45 or R-AA treatments, all patients in this study will also receive 
prednisone during the treatment period. Specifically, 5 mg prednisone will be administered orally 
twice daily for mCRPC patients, and 5 mg prednisone orally once daily will be administered for 
mCSPC patients. 
This requirement for co-adminstration of prednisone (including the dose level and frequency for 
mCRPC and mCSPC patients) is consistent with the on-label dosing requirements on R-AA. 
Abiraterone is a CYP17A1 inhibitor, and one of the side effects of CYP17A1 inhibition is a 
decrease in cortisol levels. This leads to a compensatory increase in adrenocorticotropic hormone 
(ACTH), and an accumulation of steroids with mineralocorticoid properties.  Glucocorticoids, 
such as prednisone, can suppress ACTH secretion from the anterior pituitary and thus prevent 
mineralocorticoid-related side effects (e.g., hypokalemia, hypertension, and fluid retention).   
As part of the standard ADT background, all patients in this study must also be receiving a GnRH 
analog concurrently if they have not had a bilateral orchiectomy.  ADT background will be 
recorded in the CRF.  Patients receiving a GnRH analog will record administration in a diary to 
allow assessment of compliance with ADT therapy. 
3.6 
Purpose and timing of interim analyses/design adaptations 
Not applicable as there are no plans for conducting an interim analysis.   
3.7 
Risks and benefits 
Since R-AA is already approved by the FDA for both mCRPC and mCSPC with distant 
metastases, and TAVT-45 contains the same active ingredient (abiraterone acetate), it is expected 
that patients will benefit from these treatments. Additional potential benefits of TAVT-45 over 
R-AA are described in Section 1.4, and may include less  variability of exposure, no requirement 
to take the drug on an empty stomach, and an alternative choice for patients with dysphagia or 
aversion to swallowing large pills. 
There is considerable data available on the adverse effects associated with abiraterone acetate 
from placebo-controlled clinical trials (comprising over 2000 patients from the Zytiga clinical 
program); full details are available in the Zytiga SmPC [4]. 
Based on pooled safety analyses of multiple clinical trials [3,4], the most common adverse  
reactions (≥10%) that occurred more commonly (>2%) in Zytiga treatment arm compared to 
placebo were fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, 
vomiting, upper respiratory infection, cough, and headache.  The most common laboratory 
abnormalities (>20%) that occurred more commonly (≥2%) in the Zytiga arm were anemia, 
elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, 
hyperglycemia, and hypokalemia. Grades 3-4 adverse events were reported for 53% of patients in 
the Zytiga arm and 46% of patients in the placebo arm.  Treatment discontinuation was reported 
in 14% of patients in the Zytiga arm and 13% of patients in the placebo arm.  The common adverse 
events (≥1%) resulting in discontinuation of Zytiga and prednisone were hepatotoxicity and 
cardiac disorder. 
Since TAVT-45 also contains abiraterone acetate as the active ingredient, any adverse reactions 
and their incidences are expected to be similar to those reported for Zytiga.  
One of the excipients (Soluplus) in the TAVT-45 granules has been shown to cause pseudo allergy 
symptoms in dogs given single doses, therefore this excipient may also have the potential to cause 
allergy-like reactions in humans [19]. 


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General Risks  
During cannulation, more than one attempt may be needed to insert the cannula in a vein of a 
patient, and it is possible that bruising and/or inflammation may be experienced at the site of 
cannulation.  
COVID-19 Related Risks 
The following risks and risk mitigating measures apply to this study which may be impacted by 
the ongoing SARS-CoV-2 (COVID-19) global pandemic: 
• Test Product Related Risk:    
o Based on a review of both nonclinical and clinical data, neither Zytiga nor 
TAVT-45 have immunomodulatory effects that would confer an increased risk to 
participants enrolled in the study either contracting or experiencing a more serious 
disease if infected with COVID-19.   
• General COVID-19 Related-Risk Mitigation Measures: 
o Tavanta and the clinical CRO (TMC) will work with clinical sites to document 
site-level procedures regarding COVID-related precautions for patients and staff 
(such as personal protective devices of face coverings, masks, shields, temperature 
screening, and social distancing procedures).  The study visit schedule has also 
been carefully reviewed to minimize unnecessary visits and patient exposure. 
o Tavanta and TMC will continue to assess risk during the course of the clinical 
study  due to COVID-19 impact. This includes risk assessment for the overall 
study, as well as at the country/regional levels since changes/adaptations may be 
needed at a local level depending on the local COVID-19 situation. This may 
include impacts on visit schedules, assessments performed in-person or virtually, 
and alternative options for IMP re-supply for patients. Tavanta and TMC will also 
communicate as needed with IRB/IEC and Data Monitoring Committee (DMC) 
staff.  The risk mitigation measures, where applicable, will be amended based on 
emerging government guidances. 
4 
STUDY POPULATION 
The study population will consist of mCSPC and mCRPC patients. 
The study population will be comprised of the patients who have passed screening assessments 
and who comply with eligibility criteria. Screening procedures can be repeated once to confirm 
out of range values prior to excluding a patient from participating in the study. Patients can be re-
screened only once, and no study related re-screening procedures should be performed before re-
consent by the patient. Mis-randomized patients will not be re-screened. 
4.1 
Inclusion Criteria 
1. Written informed consent obtained prior to any study-related procedure being performed  
2. Male patients at least 18 years of age or older at time of consent  
3. Pathologically confirmed adenocarcinoma of the prostate  
4. Ongoing therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist (unless 
patient has already had a bilateral orchiectomy) AND serum testosterone level <50 ng/dL at 
screening  


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5. Have either metastatic CSPC or metastatic CRPC, as defined below: 
• CSPC:   Using the American Joint Committee on Cancer (AJCC) tumor, node, 
metastasis (TNM) system, patients must have Tany Nany M+ (distant metastases) 
disease AND two of the following:  
• Gleason score of 8 or greater 
• Three or more bone scan lesions 
• Measurable visceral metastases 
• CRPC: Patients must have metastatic* disease, and must also have disease progression 
according to the recommendations of the Prostate Cancer Working Group 3 by having 
at least one of the following criteria: 
• Two rises of PSA (taken a minimum of 1 week apart) from a baseline 
measurement of at least 1 ng/mL 
• Imaging progression (CT/MRI) by RECIST 1.1 criteria or PET/CT* 
• Nuclear scan progression by 2 or more new bone lesions. 
* Note:  Metastatic disease should be documented by MRI/CT, PET/CT (including, but not 
limited to, standard of care imaging using 18F-fluciclovine, 11C-choline, or PSMA where 
approved) or bone scan. Imaging obtained within 90 days prior to the start of study 
drug/reference product will be accepted. 
6. The following prior treatment and / or surgery for prostate cancer are allowed: 
• CSPC:    
• Up to 90 days of androgen deprivation therapy (ADT) with gonadotropin-
releasing hormone (GnRH) agonists/antagonists or orchiectomy with or 
without concurrent anti-androgens prior to patients’ randomization is permitted 
• Patients may have one course of palliative radiation or surgical therapy to treat 
symptoms resulting from metastatic disease (e.g., impending cord compression 
or obstructive symptoms) if administered prior to randomization 
• Radiation or surgical therapy that was not initiated 4 weeks after the start of 
ADT or orchiectomy 
• CRPC: 
• Previous chemotherapy with docetaxel for metastatic disease with treatment 
completed at least 1 year prior to Screening 
7. Discontinuation of flutamide or nilutamide, and other anti-androgens prior to the start of study 
medication; discontinuation of bicalutamide prior to start of study medication  
8. Discontinuation of strong CYP3A4 inducers at least 4 weeks prior to start of study medication 
9. Discontinuation of radiotherapy prior to start of study medication  
10. Discontinuation of herbal supplements at least 4 weeks prior to the first dose of study 
medication and for the duration of the trial.   
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at screening  


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12. Normal organ function with acceptable initial laboratory values within the screening period:  
ANC 
≥ 1,500/µl 
Albumin 
Hemoglobin 
 ≥ 3.0g/dL 
 ≥ 9g/dL 
Platelet count 
 ≥ 100,000/µl 
Serum 
Creatinine 
≤ 3.0 x the institutional upper limit of normal 
(ULN) 
Potassium 
> 3.5 mmol/L (within institutional normal 
range) 
Bilirubin 
≤ 1.5 ULN (unless documented Gilbert's 
disease) 
SGOT (AST) 
≤ 2.5 x ULN 
SGPT (ALT) 
≤ 2.5 x ULN 
13. Life expectancy of at least 6 months at screening  
14. Patients engaged in sex with women of child-bearing potential agree to use a condom plus 
another effective contraception method.  Patients agree to use a condom when engaged in any 
sexual activity, including sex with a pregnant woman. These restrictions will apply from the 
time informed consent is provided until 3 weeks after the last dose of study medication is 
taken.  
15. Patient is willing and able to comply with all protocol requirements assessments  
4.2 
Exclusion criteria 
1. For mCSPC patients: 
• Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate 
cancer not specified as allowable treatment in Inclusion Criterion 6. For example, 
prior therapy with apalutamide or enzalutamide is prohibited as well as therapy with 
an investigational agent as described in Exclusion Criterion 16. 
2. For mCRPC patients: 
• Prior treatment with abiraterone or enzalutamide is prohibited 
• Previous chemotherapy is prohibited with exception of docetaxel treatment as specified in 
Inclusion Criterion 6. 
3. Initiation of bisphosphonate or denosumab therapy within 4 weeks prior to the start of study 
drug/reference product. Patients who are on a stable dose of these medications for at least 4 
weeks at the time of starting study drug/reference product will be eligible. 
4. Therapy with estrogen within 4 weeks prior to the start of study drug 
5. Use of systemic glucocorticoids equivalent to >10 mg prednisone daily. Patients who have 
discontinued or reduced dosing to the equivalent of ≤ 10 mg prednisone daily within 14 days 
prior to the start of study drug are eligible 
6. Known, symptomatic metastases to the brain or central nervous system involvement (patients 
with asymptomatic and neurologically stable disease for the past 4 weeks will be permitted) 
7. History of adrenal gland dysfunction defined as requiring treatment for adrenal insufficiency 
8. History of other malignancy within the previous 2 years (no longer being actively treated), 
with the exceptions of basal cell carcinoma, non-muscle invasive bladder cancer that has been 
treated and is under surveillance, or other in-situ cancers with a low likelihood of recurrence  
9. Major surgery within 4 weeks prior to the start of study drug 


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10. Known gastrointestinal disease or condition that could impair absorption inclusive of 
gastrocolic fistula, gastroenterostomy, biliary obstruction, cirrhosis, chronic pancreatitis or 
pancreatic cancer, cystic fibrosis, lactate deficiency, amyloidosis, celiac disease, Crohn’s 
disease, radiation enteritis, intestinal resection, and history of bariatric surgery 
11. Known history of human immunodeficiency virus or seropositive test for hepatitis C virus 
(HCV) or hepatitis B surface antigen (HBsAg) (note: HCV patients with undetectable viral 
load will be eligible) 
12. Poorly controlled diabetes, defined as HbA1c > 8% within the past 12 months  
13. Uncontrolled hypertension at screening 
14. History of New York Heart Association class III or IV heart failure 
15. Serious concurrent illness, including psychiatric illness, that could interfere with study 
participation 
16. Receipt of another investigational agent within 4 weeks or 5 x the treatment half-life, 
whichever is longer, of treatment start. 
17. Known hypersensitivity or allergy to abiraterone acetate, prednisone or any excipients in the 
study drugs 
18. In the opinion of the investigator, participation in the trial would prevent the patient from 
receiving local standard-of-care treatment for metastatic prostate cancer, if clinically 
indicated, after completion of the trial   
19. Other condition which, in the opinion of the Investigator, would preclude participation in this 
trial. 
5 
TREATMENT 
5.1 
Study treatment: investigational and control drugs 
Tavanta will supply the following study drug: 
Investigational treatment 
•   TAVT-45 (250 mg abiraterone acetate) - Granules for Oral Suspension 
Tavanta will supply the reference treatment which will be centrally sourced and supplied. 
Reference treatment 
•   R-AA (reference abiraterone acetate [Zytiga]) 500 mg tablets 
5.2 
Additional treatments 
In addition to the study drugs described above in Section 5.1, Tavanta or designee will also supply 
prednisone (5 mg tablets). Specifically, 5 mg prednisone will be administered orally twice daily 
for mCRPC patients, and 5 mg prednisone orally once daily will be administered for mCSPC 
patients. 
All patients must also be receiving a GnRH analog concurrently if they have not had a bilateral 
orchiectomy.  GnRH analogs will not be provided by Tavanta and will be sourced locally through 
the patient’s current prescription. 


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5.3 
Treatment arms 
In this study, patients will be randomized 1:1 to one of two groups and treated for 84 days: 
• TAVT-45:  Administered twice daily as 1 x sachet containing TAVT-45 granules (250 mg 
abiraterone acetate) + Prednisone (5 mg once or twice daily, depending on prostate cancer 
population) 
• R-AA once daily:  Administered once daily as (2 x 500 mg Zytiga tablets) + Prednisone 
(5 mg once or twice daily, depending on prostate cancer population) 
5.4 
Treatment assignment and randomization 
All eligible patients will be randomized 1:1 to one of the two treatment arms.  Randomization will 
be stratified by prostate cancer population (CSPC vs CRPC; n=54 per cancer population) and 
baseline testosterone (<10 vs ≥ 10 ng/dL). 
Patients will be assigned a Subject Number upon screening. Eligible patients will be randomized 
via an Interactive Response Technology (IRT) system. Sites will contact the IRT system only after 
confirming all eligibility criteria and receiving the screening testosterone value that is needed for 
stratification (see Table 1). The IRT will assign the patient to the appropriate treatment arm and 
provide a medication number that will be linked to the different treatments. A separate medication 
list will be produced by or under the responsibility of Tavanta using a validated system that 
automates the random assignment of medication numbers to packs containing the study drug(s). 
5.5 
Treatment blinding 
This study is open label.  
5.6 
Treating the subject 
5.6.1 
Subject numbering 
Each patient is uniquely identified by a Subject Number. Once assigned to a patient, the Subject 
Number will not be reused. Patients may be re-screened once. In this case, the IRT can be used to 
request the initial Subject Number in order to link the re-screening to the original screen of that 
patient. Patients who are mis-randomized cannot be re-screened. 
5.6.2 
Dispensing the investigational treatment 
Each study site will be supplied by Tavanta or designee with sachets containing TAVT-45 and R-
AA tablets. A unique medication number is printed on each part of the label which corresponds 
to test or reference treatment. 
5.6.3 
Handling of study treatment 
Study Investigational treatment must be received by a designated staff member at the study site, 
handled and stored safely and properly, and kept in a secured location. Upon receipt, all 
investigational treatment should be stored according to the instructions specified on the labels.  
TAVT-45 granules should be stored at room temperature in the aluminum foil sachet. R-AA 
tablets should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted in the range from 
15°C to 30°C (59°F to 86°F). Clinical supplies are to be dispensed only in accordance with the 
protocol. Any excursions or lack of compliance should be reported to Tavanta or designee. 
Medication labels will include storage conditions for the study treatment and the medication 
number and will be compliant with labeling regulations. 


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The qualified site personnel must maintain an accurate record of the shipment and dispensing of 
study treatment. Monitoring of drug accountability will be performed by a field monitor during 
site visits and at the completion of the trial. At the conclusion of the study and as appropriate 
during the study, all investigational treatments will be reconciled at the site and depot level. 
Instructions for the final disposition of all unused study medication will be provided to each site 
in advance of site closure.  
5.6.4 
Instructions for prescribing and taking study treatment 
Study treatments TAVT-45 and R-AA [Zytiga] tablets) will be administered orally each day from 
Day 1 to Day 84.  
TAVT-45 will be taken twice daily (approximately every 12 hours) and may be taken without 
respect to meals.  An exception applies to those patients included in the serial pharmacokinetic 
cohort.  Patients participating in the serial blood draws on Days 1 and 9 will administer TAVT-45 
in the fasted state (minimum of 8 h overnight fast) on these days and may resume normal meal 
schedules 2 h after administration of the TAVT-45 on these days.  
Each TAVT-45 sachet contains 250 mg abiraterone acetate, and excipients that ensure abiraterone 
acetate disperses instantaneously in water or specified juice. For a 250 mg dose, 1 granule sachet 
should be reconstituted in tap water or specified juice and the resulting suspension immediately 
administered orally. Reconstitution of the granules can be obtained by stirring the suspension with 
a spoon for 3 minutes. The reconstituted suspension should be taken immediately after 
reconstitution.  Patients will receive training and a medication preparation guide to ensure correct 
preparation and administration. At visits when trough abiraterone samples are obtained (see Table 
1), the reconstitution fluid (water or juice) used for the last dose will be recorded in the eCRF. 
For R-AA, tablets should be taken once daily, either ≥ 1 hour before or ≥ 2 hours after a meal, and 
swallowed whole with water. For a 1000 mg dose, 2 tablets (containing 500 mg abiraterone 
acetate) should be taken together. 
Patients will be instructed to record administration of study medications in a dosing diary.  This 
is inclusive of TAVT-45, R-AA, prednisone and GnRH analog, if applicable.  The patient will 
record the date and time of each administration of each medication.  For TAVT-45, the patient 
will also record the fluid (water or specified juice) used for reconstitution. 
The investigator should promote compliance by instructing the patient to attend the study visits as 
scheduled and by stating that compliance is necessary for the patient’s safety and the validity of 
the study. The patient should be instructed to contact the investigator if he is unable for any reason 
to attend a study visit as scheduled. 
5.6.5 
Permitted dose adjustments and interruptions of study treatment 
There will not be any planned permitted adjustments of dose strength and frequency.  Patients 
should take TAVT-45 and R-AA as per protocol.  
However, if needed due to adverse events, study medication may be temporarily or permanently 
discontinued at the discretion of the Investigator based on the toxicity management guidance 
described below related to hepatotoxicity and Grade ≥ 3 toxicities, which aligns with Zytiga 
prescribing information [3, 4]. Investigators should consult with the Medical Monitor for 
questions/clarifications as needed.  
• Hepatotoxicity:  If at any time during the trial, the ALT or AST rises above 5x ULN, or 
total bilirubin rises above 3x ULN, treatment with TAVT-45 or R-AA should be 
discontinued immediately and the patient should be discontinued from the study. As noted 


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above, dose reductions are not applicable for this clinical trial, as only one strength of each 
study medication (TAVT-45 and R-AA) are supplied to patients. Liver function should be 
closely monitored as part of adverse event monitoring. 
• Grade ≥ 3 toxicities of hypertension, hypokalaemia, oedema and other non-
mineralocorticoid toxicities: If at any time during the trial, a patient experiences Grade ≥ 
3  hypertension, hypokalaemia, oedema or other non-mineralocorticoid toxicities 
(according to the National Cancer Institute Common Terminology Criteria for Adverse 
Events [CTCAE], Version 5.0 [20]), treatment should be withheld and appropriate medical 
management should be instituted. Treatment with TAVT-45 or R-AA should not be 
reinitiated until symptoms of the toxicity have resolved to Grade 1 or baseline.  
All actions with respect to study drug dosing in relation to an AE must be documented 
appropriately within the CRF. 
5.6.6 
Rescue medication 
Not applicable. 
5.6.7 
Concomitant medication 
In addition to the TAVT-45 or R-AA treatments, all patients in this study will also receive 
prednisone during the treatment period. Specifically, 5 mg prednisone will be administered orally 
twice daily for mCRPC patients and 5 mg prednisone orally once daily will be administered for 
mCSPC patients. 
Per protocol, all patients in this study should also be taking a GnRH analog concurrently or should 
have had bilateral orchiectomy. 
Bisphosphonate usage is allowed only if patients are on the medication at a stable dose and 
regimen for 4 weeks prior to Study Day 1 (see Exclusion Criterion #3). 
The investigator should instruct the patient to notify the study site about any new medications 
over-the-counter drugs, supplements, and vitamins administered after the patient is enrolled into 
the study. All medications (other than study treatment), procedures and significant non-drug 
therapies (including physical therapy and blood transfusions) must be recorded on the CRF. The 
reason, name of the drug, procedure or non-drug therapy should be listed.  
Since androgen deprivation treatment may prolong the QT interval, caution is advised when 
administering abiraterone acetate with medicinal products known to prolong the QT interval or 
medicinal products able to induce torsades de pointes such as class IA (e.g. quinidine, 
disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal 
products, methadone, moxifloxacin, antipsychotics, etc. 
Use of spironolactone with abiraterone acetate is not recommended, since spironolactone binds to 
the androgen receptor and may increase PSA levels. 
5.6.8 
Prohibited medication (interaction with other medicinal products 
and other forms of interaction) 
Refer to the Inclusion and Exclusion Criteria regarding medications that are prohibited, or must 
be discontinued, prior to the start of study drug and throughout the study (see Sections 4.1 and 
4.2). 


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Concomitant use of a strong CYP3A4 inducer should be avoided (see Section 5.6.8.2) and caution 
should be exercised if a CYP2D6 substrate with a narrow therapeutic index cannot be avoided 
(see Section 5.6.8.3). 
5.6.8.1 
Abiraterone acetate contraindications 
Abiraterone acetate can cause fetal harm and potential loss of pregnancy based on animal studies. 
However, it is not indicated for use in women.   
5.6.8.2 
Effects of other medicinal products on abiraterone acetate   
Cytochrome P450 inhibitor 
In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of 
CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone. 
Cytochrome P450 inducers 
In a dedicated drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, 
decreased exposure of abiraterone by 55%. This reduced exposure can be anticipated to decrease 
the efficacy of abiraterone. Thus, concomitant strong CYP3A4 inducers should be avoided during 
abiraterone treatment. Notable examples of strong CYP3A4 inducers are apalutamide, 
carbamazepine, enzalutamide, mitotane, phenobarbital, phenytoin, rifabutin, rifampicin, 
rifapentine and St John's wort [4,21]. 
5.6.8.3 
Effects of abiraterone acetate on other medicinal products  
CYP2D6 Substrate 
Abiraterone is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6.  In a CYP2D6 
drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were 
increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone 
acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone 
acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine).  If 
alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 
substrate drug. 
CYP2C8 Substrate 
Abiraterone is an inhibitor of the hepatic drug-metabolizing enzyme CYP2C8.  In a CYP2C8 
drug-drug interaction trial, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% 
when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate.  
Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate 
with a narrow therapeutic index if used concomitantly with abiraterone.  Investigators may consult 
with the Medical Monitor for identification of CYP2C8 substrates with narrow therapeutic index.  
5.6.9 
Discontinuation of study treatment 
Patients may voluntarily discontinue study treatment or the study for any reason at any time. The 
investigator should discontinue study treatment for a patient if, on balance, he/she believes that 
continuation would be detrimental to that patient’s well-being. Study treatment must be 
discontinued under the following circumstances: 
• Withdrawal of informed consent 
• Patient’s request to terminate treatment (in this case, the patient may choose to discontinue 
study treatment, but remain in the study to be followed for safety and undergo study 
procedures through the follow-up period) 


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• Any AE, clinically relevant change(s) in a safety parameter, or other medical condition or 
situation that occurs such that continued participation in the study would not be in the 
participant’s best interest. This includes ALT or AST rises above 5x ULN, or total bilirubin 
rises above 3x ULN, at any time during the study as described in Section 5.6.5. 
• Use of prohibited treatment without approval from the Medical Monitor  
• Any other protocol deviation that results in a significant risk to the patient’s safety 
• Study is terminated by the Sponsor or local health authority, IRB, or IEC 
For patients who discontinue study treatment, a CRF should be completed, giving the date and 
primary reason for stopping study treatment.  In the event that the decision is made to permanently 
discontinue the study treatment, the patient will be withdrawn, and the ET visit should be 
conducted. Reasonable efforts should be made to have the patient return for this follow-up visit. 
5.7 
Withdrawal of consent 
Patients may be considered discontinued if they state an intention to withdraw, fail to return for 
visits, or become lost to follow-up for any other reason. 
If premature discontinuation occurs for any reason, the investigator must make every effort to 
determine the primary reason for a patient’s premature discontinuation from the study and record 
this information on the CRF. Patients may voluntarily withdraw consent to participate in the study 
for any reason at any time. 
Withdrawal of consent occurs when a patient does not want to participate in the study anymore, 
that is, the patient does not want any further visits, assessments, or study-related contact and does 
not allow analysis of already obtained biologic material. Study treatment must be discontinued, 
and no further assessments conducted. All biological material that has not been analyzed at the 
time of withdrawal must not be used. Further attempts to contact the patient are not allowed unless 
safety findings require communicating or follow-up. The data collected on the patient to the point 
of withdrawal remains part of the study database and may not be removed. 
5.8 
Lost to follow-up 
For patients whose status is unclear because they fail to appear for study visits without stating an 
intention to withdraw, the investigator should show "due diligence" by contacting the patient, 
family or family physician as agreed in the informed consent and by documenting in the source 
documents steps taken to contact the patient, e.g. dates of telephone calls, registered letters, etc. 
A patient should not be formally considered lost to follow-up until his scheduled End-of-Study 
visit would have occurred. 
5.9 
Emergency breaking of assigned treatment code 
Not applicable as the study is open label. 
5.10 
Study completion and post-study treatment 
End of study is defined as the date of the last patient last visit (i.e., the Visit 10 follow-up phone 
call for patients completing the trial as planned, or the Early Termination Visit for patients who 
are treated but discontinue prior to completing the Day 84 visit [see Table 1 below]). 
Information on the patient’s completion of dosing during the Treatment Period, or premature 
discontinuation and the reason for discontinuation will be recorded on the appropriate form of 
CRF. In any case, the investigator or site staff must contact as soon as possible to record the 
patient’s study completion and/or discontinuation. 


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The investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study or must refer them for appropriate ongoing care. This care may include 
initiating another treatment outside of the study as deemed appropriate by the investigator. 
There is no post-trial access to study medication after patients complete this trial; instead 
investigators will prescribe the local standard-of-care treatment for metastatic prostate cancer, if 
clinically indicated. 
5.11 
Early study termination 
The study can be terminated at any time for any reason by Tavanta. Should this be necessary, the 
patient must be seen as soon as possible and treated as a prematurely withdrawn patient. The 
investigator may be informed of additional procedures to be followed in order to ensure that 
adequate consideration is given to the protection of the patient’s interests. The investigator will 
be responsible for informing the Institutional Review Board (IRBs) or Independent Ethics 
Committee (IECs) of the early termination of the trial. 
6 
VISIT SCHEDULE AND ASSESSMENTS 
Table 1 lists all of the assessments and indicates with an “X” when the assessments should be 
performed at the designated time points. Patients should be seen for all visits on the designated 
day or as closely as possible to the original planned visit schedule. Missed or rescheduled visits 
should not lead to automatic discontinuation. 
If patients refuse to return for these assessments or are unable to do so, every effort should be 
made to contact them or a knowledgeable informant by telephone to determine the reason. 
Attempts to contact the patient should be recorded in the source documentation. 
Screening will be flexible in duration of up to 28 days before first dosing, during which time the 
patient will sign the informed consent form (ICF) to participate in the study before any protocol-
specified procedures or assessments are initiated. Patients evaluated at screening for eligibility 
should not be screen failed on the basis of a medication requiring washout, unless the patient will 
be unable to complete the washout in the appropriate time frame before randomization.  Upon 
meeting all inclusion/exclusion criteria set forth in the protocol, patients will be randomized in a 
1:1 fashion to receive either TAVT-45 250 mg twice daily (approximately every 12 hours) or 
R-AA 1000 mg once daily either ≥ 1 hour before or ≥ 2 hours after a meal. All patients should 
also receive prednisone together with a gonadotropin-releasing hormone (GnRH) analog 
concurrently or should have had bilateral orchiectomy. The mCSPC patients will receive 
prednisone 5 mg orally once daily, while the mCRPC patients will receive prednisone 5 mg orally 
twice daily.  Randomization will be stratified by prostate cancer population (CSPC vs CRPC) and 
baseline testosterone (<10 vs ≥ 10 ng/dL). All patients will be treated for 84 days (12 weeks).  
Patients will return to their clinics on Days 9, 10, 28, 56 and 84 for assessments and evaluations 
of safety and efficacy, including testosterone, PSA, and abiraterone trough concentrations. 
Patients may return to the clinic or may visit a local laboratory for evaluation of liver function 
tests on Days 42 and 70.  Blood samples for testosterone will be taken between the hours of 7-10 
in the morning. A pharmacokinetic sub-study will be conducted in a cohort of up to 8 patients 
receiving TAVT-45. Pharmacokinetic profiles over the dosing interval will be obtained on Day 1 
(first dose) and on Day 9 (steady state).  For all patients, a follow-up phone call will also be made 
approximately one week after the last dose for AE assessments.  


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Table 1                      Assessment schedule 
 
Screening 
(Day -28  
to -1) 
Day 1 
Day 9 
(+2) 
Day 10 
(+2) 
Day 28 
(+/-1) 
 
Day 42 
(+/- 3) 
Day 56   
(+/-1) 
 
Day 70 
(+/- 3) 
Day 84 
  (+/-1) 
 
Follow-up 
Visit1 
(Day 91 
(+/-4) 
Early 
Termination 
(ET) Visit2 
Visit number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
ET 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
Medical history/diagnosis 
X 
X 
 
 
 
 
 
 
 
 
 
Physical examination3 
X3 
X 
 
 
X 
 
X 
 
X 
 
X 
ECOG 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
12-lead ECG4 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
Body weight and height5 
X5 
X 
 
 
X 
 
X 
 
X 
 
X 
Clinical laboratory tests6 
X6 
X 
X 
 
X 
 
X 
 
X 
 
X 
Hepatotoxicity Monitoring7 
 
 
 
X 
 
X 
 
X 
 
 
 
Serum testosterone8 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
PSA8 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
Serial Pharmacokinetic Sampling9 
 
X 
X 
 
 
 
 
 
 
 
 
Abiraterone trough 
concentrations10 
 
 
X 
 
X 
 
X 
 
X 
 
 
Prior/concomitant medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events/SAEs11 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
X12 
 
 
 
 
 
 
 
 
 
Drug dispensation 
 
X 
 
 
X 
 
X 
 
 
 
Drug return/compliance/diary 
review  
 
 
 
 
X 
 
X 
 
X 
 
X 
 
 
 


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1. 
For the follow-up visit, a phone call should be made approximately one week after the last dose for AE assessments 
2. 
If patients are randomized and treated, but discontinue prior to completing the Day 84 visit, then an early termination visit should be scheduled. 
3. 
Physical examination at screening includes examination of general appearance, skin, lungs, heart, abdomen, lymph nodes, extremities and vascular system.  Abbreviated 
examinations thereafter to include targeted assessment(s) of the body systems or organs, as indicated by patient symptoms, AEs, or other findings. 
4. 
ECG to be completed after the patient has been in the supine position for a minimum of 5 minutes.  ECG to be conducted before vital signs or blood draws if scheduled at the 
same visit. 
5. 
Height without shoes is measured at the screening visit only.  
6. 
Laboratory safety tests include panels for haematology, clinical chemistry, and urinalysis. At screening only, patients will also be tested for HCV and HBsAg. 
7. 
Transaminases (ALT and AST) along with bilirubin will be obtained to monitor liver function.  These assessments may be completed by a local laboratory and reported to the 
clinical site, if necessary.   
8. 
Testosterone and PSA blood samples are to be collected between 7 and 10 in the morning. 
9. 
Completed only in a cohort of up to 8 patients randomized to TAVT-45 at select site(s) only. Patients are to take their TAVT-45 morning dose in the fasted state (following an 
overnight fast of at least 8 h) on Days 1 and 9 and will continue to fast for 2 h after morning dose administration after which a normal meal schedule can be resumed. The 
morning dose administered on Days 1 and 9 will be reconstituted with water. Allowable windows for PK sample collection are provided in Section 6.6. 
10. All patients will have pre-dose blood samples collected. However, a separate sample on Day 9 is not needed if this Day 9 pre-dose sample is already being collected as part of 
the serial PK sampling cohort.  Reconstitution fluid used for the previous dose (water or specified juice) will be recorded in the eCRF on days of trough sampling. 
11. All AEs /SAEs occurring after the patient has provided informed consent must be reported. 
12. This randomization step will be the last activity to occur during the Screening window. Sites will contact the IRT system only after confirming all eligibility criteria and 
receiving the screening testosterone value that is needed for stratification. 
 


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6.1 
Information to be collected on screen failures 
Patients may discontinue from the study prior to randomization. These patients are considered 
screen failures. If a patient discontinues before entering the treatment period at baseline, the reason 
for not being randomized will be entered on the CRF.  
All patients who have signed informed consent and are randomized into the Treatment Period of 
the study will have all AEs occurring after informed consent is signed recorded on the Adverse 
Event CRF.   
 
6.2 
Subject demographics/other baseline characteristics 
Patient demographic, baseline characteristic, and medical history data must be collected on all 
patients and recorded in the CRF. Also, medical history relevant to prostate cancer (such as date 
of diagnosis and Gleason score) should also be recorded. Whenever possible, diagnoses and not 
symptoms will be recorded. Investigators will have the discretion to record abnormal test findings 
on the medical history CRF whenever in their judgment. 
 
6.3 
Treatment exposure and compliance 
All dates of study treatment dispensing will be recorded on the appropriate CRF. Drugs 
administered prior to start of treatment and other drugs/procedures continuing or started during 
the study treatment period will be entered in the Prior/Concomitant medications CRF.  
Compliance (adherence) is expected to be 100%. During each Treatment Period, the number of 
granule sachets or tablets dispensed and returned will be counted to determine compliance with 
dosing regimen for TAVT-45, R-AA and prednisone. Compliance (adherence) will also be 
assessed by a study monitor using information provided by the authorized site personnel. 
 
6.4 
Contraception   
All sexually active patients must use a condom. Male patients who are sexually active with a 
female partner of child-bearing potential* must use, with their partner, a condom plus an approved 
method of highly effective contraception from the time of informed consent until 3 weeks after 
the last dose of study medication.   
A highly effective method of contraception is defined as one that has no higher than a 1% failure 
rate. In this study, the only highly effective methods of contraception are: 
  
• 
Partner’s use of combined (oestrogen and progestogen-containing) hormonal 
contraception:   
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
• 
Partner’s use of progestogen-only hormonal contraception associated with inhibition 
of ovulation:   
• 
Oral   
• 
Injectable/implantable   
• 
Intrauterine hormone-releasing system  
• 
Partner’s use of implantable intrauterine device  


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• 
Surgical sterilization (for example, vasectomy or partner’s bilateral tubal occlusion, 
provided that partner is the sole sexual partner of a study patient of child-bearing 
potential and that the vasectomized partner has received medical assessment of the 
surgical success)  
Alternatively, true abstinence is acceptable when it is in line with the patient’s preferred and usual 
lifestyle. Periodic abstinence (eg, calendar, ovulation, symptothermal, post ovulation methods for 
the female partner) and withdrawal are not acceptable methods of contraception. If a patient is 
usually not sexually active but becomes active, they, with their partner, they must comply with 
the contraceptive requirements detailed above.  
*For clarification, a women of childbearing potential (WOCBP) is defined as any female who 
has experienced menarche and who has not undergone successful surgical sterilization 
(hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal 
(defined as amenorrhea ≥12 consecutive months; or women on hormone replacement therapy 
with documented serum follicle-stimulating hormone level ≥35 mIU/mL). 
6.4.1 
Exposure to Partners During the Study  
There is a significant risk of drug exposure through the ejaculate (which also applies to 
vasectomized males) that might be harmful to the sexual partners (both male and female), 
including pregnant partners of male patients. Therefore, a condom should be used by all male 
subjects from the time of informed consent until three weeks after the last dose of study 
medication.  
6.4.2 
Sperm Donation  
Male patients should not donate sperm from the time of informed consent until three weeks after 
the last dose of study medication. 
6.5 
Efficacy assessments 
6.5.1 
Serum testosterone 
Samples for serum testosterone during the Screening period will be taken between 7 am and 
10 am.  The result of this serum testosterone will be used to qualify the patient for participation 
in the trial and to randomize eligible patients with stratification by testosterone level.   
Samples for serum testosterone assessment points during the treatment period as specified in 
Table 1 should be taken between 7 and 10 in the morning and be analyzed using a validated and 
ultrasensitive testosterone assay at a central laboratory with a lower limit of quantification 
(LLOQ) of 0.1 ng/dL.  The serum testosterone obtained pre-dose on Day 1 will be the baseline 
value for any testosterone change from baseline comparisons during the treatment period.  
6.5.2 
Prostate-specific antigen 
Samples for PSA will be collected as specified in Table 1 should be taken between 7 and 10 in 
the morning and analyzed using a validated and ultrasensitive PSA assay at a central reference 
laboratory.  
6.5.3 
Abiraterone trough concentrations 
Blood samples for abiraterone trough concentrations will be collected on Days 9, 28, 56 and 84 
(taken before dosing) for all patients. Study staff will remind patients to withhold their morning 
study medication administration on these visit days.  The reconstitution fluid (water or specified 
juice) used for administration of the previous dose will be recorded in the eCRF on days of trough 
sampling. 
Abiraterone trough concentrations will be analyzed using a validated bioanalytical method.  
 


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6.6 
Pharmacokinetics 
For a cohort of up to 8 patients randomized to TAVT-45 granules and participating in the serial 
PK sampling on Day 1 and Day 9, blood samples (approximately 4 mL) will be collected at the 
following times: 
• Day 1: at pre-dose (± 30 min), and 0.25 (± 5 min), 0.5 (± 5 min), 0.75 (± 5 min),  
1 (± 5 min), 1.5 (± 10 min), 2 (± 10 min), 3 (± 10 min), 4 (± 30 min), 8 (± 30 min),  
10 (± 30 min), and 12 (± 30 min) hours post-dose and before the scheduled evening dose  
• Day 9: at pre-dose (± 30 min), and 0.25 (± 5 min), 0.5 (± 5 min), 0.75 (± 5 min),  
1 (± 5 min), 1.5 (± 10 min), 2 (± 10 min), 3 (± 10 min), 4 (± 30 min), 8 (± 30 min),  
10 (± 30 min), and 12 (± 30 min) hours post-dose and before the scheduled evening dose 
Patients will be in the fasted state (overnight fast of at least 8 h) at the time of morning TAVT-45 
administration and will remain fasted for 2 hours after morning dose administration after which 
time the normal meal schedule may be resumed. The morning dose of TAVT-45 granules will be 
reconstituted with water on Days 1 and 9.  Abiraterone concentrations in these serial samples will 
be analyzed using a validated bioanalytical method.   
6.7 
Safety 
All safety assessments should be done prior to study treatment administration. Appropriate safety 
assessments should be repeated after the dose is administered as per Table 1. 
Safety assessments will include: 
• 
Clinical chemistry and hematology  
• 
Vital signs 
• 
Electrocardiograms 
• 
Physical examination 
• 
AEs 
6.7.1 
Clinical laboratory assessments 
At Screening only, patients will be tested for HCV and HBsAg to determine eligibility. 
At Screening and during the study, laboratory safety tests will also be performed according to the 
time schedule presented in Table 1.  The following parameters will be collected: 
• 
Haematology:  Haemoglobin, Platelet Count, White Blood Cells, including absolute 
neutrophil count (ANC) 
• 
Clinical Chemistry: Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase 
(ALP), Aspartate Aminotransferase (AST), Bilirubin (Total), Bilirubin (Direct) (only 
if Total is elevated), Creatine Kinase, Creatinine, Gamma Glutamyl Transferase, 
Glucose (Fasting), Lactate Dehydrogenase, Potassium, Phosphate (Inorganic), Protein 
(Total), Sodium, Urea 
• 
Urinalysis: Bilirubin, Blood, Glucose, Ketones, Leukocytes, Nitrites, pH, Protein, 
Specific gravity, Urobilinogen 
In cases where laboratory findings are outside the normal range and the investigator believes that 
the results may be of clinical significance, repeat sampling may be requested as clinically 
indicated. If the abnormal finding is clinically significant, appropriate actions will be taken e.g., 


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the patient may not be entered into the study or the patient may be withdrawn from the study. The 
patient will be referred to their general practitioner or other appropriate provider for further care.  
Any clinically significant abnormality, including changes from baseline, must be reported as an 
AE. 
Additional blood and/or urine samples may be taken for safety tests. Furthermore, additional 
assays outside those specified in the protocol may be performed for safety reasons as requested 
by the investigator. 
6.7.2 
Vital signs 
Vital signs will be performed according to the time schedule presented in Table 1. Vital sign 
assessments will include blood pressure, heart rate, respiratory rate and body temperature; body 
weight will also be measured according to the time schedule presented in Table 1, with the patient 
lightly clothed and without shoes. Patient height (without shoes) will be measured at Screening 
only. 
If a patient shows an abnormal assessment at any stage, repeat measurements may be made and 
the abnormality followed to resolution if required. Additional measurements may be taken as 
deemed necessary by the investigator 
Any clinically significant abnormality, including changes from baseline, must be reported as an 
AE. 
6.7.3 
Electrocardiograms 
Twelve-lead ECGs will be conducted at Screening, after the patient has been in the supine position 
for a minimum of 5 min. If possible, it is preferred that ECGs be conducted prior to vital sign 
assessments or blood draws if scheduled for the same visit. 
6.7.4 
Physical examination 
The physical examination will include the examination of general appearance, skin, lungs, heart, 
abdomen, lymph nodes, extremities and vascular system. Patients will have a full physical 
examination at Screening, and then abbreviated exams during each subsequent visit that will be 
targeted assessment(s) of the body systems or organs, as indicated by patient symptoms, AEs, or 
other findings. 
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present before signing the ICF must be included in the 
relevant medical history CRF. Significant findings made after signing the ICF which meet the 
definition of an AE must be recorded in the Adverse Event CRF. 
7 
 SAFETY MONITORING 
7.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and 
unintended sign, including clinically significant abnormal laboratory findings, symptom or 
disease) in a clinical investigation patient after providing informed consent for participation in 
the study until the end of study visit. Therefore, an AE may or may not be temporally or causally 
associated with the use of a medicinal (investigational) product. 
An adverse reaction is any untoward and unintended responses to study treatment related to any 
dose administered.  


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An unexpected adverse reaction is an adverse reaction in which the nature or severity is not 
consistent with the Reference Safety Information (RSI) outlined in the IB (for TAVT-45) or 
SmPC (for R-AA). 
All AEs spontaneously reported by the patient or reported in response to the open-ended and 
non-leading verbal questioning from the study personnel (e.g., “How are you feeling?” “Have 
you had any health problems since the previous visit/you were last asked?”), or revealed by 
observation will be collected and recorded in the CRF.  
Abnormal laboratory values or test results constitute AEs only if they are clinically significant, 
which is defined as fulfilling at least one of the following criteria: 
• 
they induce clinical signs or symptoms, 
• 
they fulfil any of the criteria for a serious adverse event, 
• 
they require therapy 
• 
they cause a dose reduction, or interruption or discontinuation of a medication 
• 
they cause study withdrawal 
• 
they require additional investigation 
Adverse events must be recorded in the Adverse Events CRF, accompanied by the following 
information: 
• 
the severity (intensity) grades according to the National Cancer Institute Common 
Terminology Criteria for Adverse Events (CTCAE), Version 5.0 or higher that has 
unique clinical descriptions of severity for each adverse event, but follows the 
following guidelines: 
• 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated.  
• 
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; 
limiting age appropriate instrumental activities of daily living (ADL) (preparing 
meals, shopping for groceries or clothes, using the telephone, managing money, 
etc).  
• 
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL (bathing, dressing and undressing, feeding self, using the toilet, 
taking medications, and not bedridden).  
• 
Grade 4: Life-threatening consequences; urgent intervention indicated.  
• 
Grade 5: Death related to AE.  
• 
its relationship to the study treatment (TAVT-45 or R-AA). See NOTE below 
• 
Related: There is a reasonable possibility that the event may have been caused 
by the study treatment. 
• 
Not related: The adverse event can be readily explained by other plausible 
factors such as medical history; lack of efficacy / worsening of the treated 
condition; concomitant medication, or no obvious temporal relationship exists 
between the study medication and the adverse event.  
• 
its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved must be reported 
• 
outcome 


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• 
whether it constitutes a serious adverse event and which seriousness criteria have been 
met 
• 
action taken regarding investigational treatment. 
 
NOTE: Causality (relationship between each AE and study treatment) must be carefully 
considered to answer a question:  Is there a reasonable possibility that the AE or SAE may have 
been caused by the study treatment? The investigator must endeavor to obtain sufficient 
information to support the causality of the AE and give their opinion of the causal relationship 
between each AE and study treatment considering the following (list not exhaustive): time latency, 
concurrent conditions (including disease under study), concomitant medications, dechallenge 
(even resolves or improves after interruption of study treatment) or rechallenge (event reappears 
or worsens when dosing is resumed) and pharmacological activity of study treatment. 
Once an AE is detected, it must be followed until its resolution, until it is judged to be permanent, 
or it becomes unlikely that any additional information can be obtained. Assessment must be made 
at each visit (or more frequently, if necessary) of any changes in severity, the suspected 
relationship to the study drug, the interventions required to treat it, and the outcome. 
Whenever possible, diagnoses should be given when signs and symptoms are due to a given 
etiology. In such cases, the diagnosis should be documented as the adverse event. Associated signs 
or symptoms not generally attributed to a given diagnosis should be recorded separately. 
If deterioration in a laboratory value, vital sign, ECG or other safety assessment is associated with 
clinical signs and symptoms, the sign or symptom will be reported as an AE and the associated 
laboratory result or other finding will be considered as additional information. Wherever possible 
the reporting investigator uses the clinical, rather than the laboratory term (e.g, anaemia versus 
low haemoglobin value). In the absence of clinical signs and symptoms, clinically relevant 
deteriorations in non-mandated parameters should be reported as AE(s).  
Deterioration of eg. laboratory value or other safety assessment that is unequivocally due to 
disease progression should not be reported as an AE.  
To ensure patient safety, every AE, regardless of causality, occurring after the patient has provided 
informed consent and until the Follow-up Visit must be captured via the eCRF as soon as possible 
on learning of its occurrence. AE follow up information will be collected as required until either 
the event is considered as resolved, agreed as not possible to resolve or until the patient is lost to 
follow up.     
7.2 
Serious adverse events 
7.2.1 
Definition of SAE 
An AE or suspected adverse reaction is considered serious (SAE) if, in the view of either the 
investigator or sponsor, it meets any one of the following criteria: 
• 
Death. 
• 
Life-threatening.  Life-threatening means that the patient was at immediate risk of death 
from the reaction as it occurred, i.e., it does not include a reaction which hypothetically 
might have caused death had it occurred in a more severe form. 
• 
In-patient hospitalization or prolongation of existing hospitalization.  Note: an 
emergency room or urgent care visit without hospital admission will not be recorded as 
an SAE under this criterion, nor will hospitalization for a procedure scheduled or 


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planned before signing of informed consent, or elective treatment of a pre-existing 
condition that did not worsen from baseline. However, unexpected complications 
and/or prolongation of hospitalization that occur during elective surgery should be 
recorded as AEs and assessed for seriousness. Admission to the hospital for social or 
situational reasons (i.e., no place to stay, live too far away to come for hospital visits, 
respite care) will not be considered serious. 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
• 
Congenital anomaly/birth defect. 
• 
Important medical event.  An important medical event is an event that may not result 
in death, be life-threatening, or require hospitalization but may be considered an SAE 
when, based upon appropriate medical judgment, it may jeopardize the patient or 
patient and may require medical or surgical intervention to prevent one of the outcomes 
listed in the definitions for SAEs.  Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in in-patient hospitalization, or the 
development of drug dependency or drug abuse. All malignant neoplasms will be 
assessed as a medically important event if other seriousness criteria are not met. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. All AEs (serious and non-serious) are captured on the eCRF. 
7.2.2 
SAE reporting 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until the Follow-up Visit must be reported to Tavanta or 
designee within 24 hours of learning of its occurrence (see Safety contact information below). 
Any SAEs experienced after this period should only be reported to Tavanta or designee if the 
investigator suspects a causal relationship to study treatment. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at a 
different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event. 
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form; all applicable sections of the form must be completed in order to provide a clinically 
thorough report.  At a minimum, the following information should be provided: 
• Sponsor study number 
• Subject number  
• Valid reporter (reporter and PI signature) 
• Event term (Diagnosis if available, symptoms if not) 
• Suspected study medications (IMPs) 
• Causality assessment 
 


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Safety Contact Information: 
TMC Pharma Services Ltd (Pharmacovigilance) 
E-mail: tavanta@tmcpharma.com  
Telephone (24/7): +44 1252 84 22 55 
Facsimile USA: +1 617 6636 222  
Fax Europe/ROW: +44 1189 00 78 22 
7.2.3 
Expedited Reporting  
The sponsor/designee will report all relevant information about suspected unexpected serious 
adverse reactions (SUSARs) that are fatal or life-threatening as soon as possible to the FDA, 
applicable regulatory authorities in all the concerned countries, and to the Central Ethics 
Committee(s), and in any case no later than seven days after knowledge by the sponsor/designee 
of such a case.    
All other serious cases and any significant new information on an already reported case received 
by the sponsor meeting SUSAR criteria will be reported to the FDA, applicable regulatory 
authorities concerned and to the Central Ethics Committee(s) concerned as soon as possible but 
within a maximum of 15 days of first knowledge by the sponsor/designee.  
The sponsor/designee will also report any additional expedited safety reports required in 
accordance with the timelines outlined in country-specific legislation. 
The sponsor/designee will also inform all investigators as required per local regulation.  
The requirements above refer to the requirements relating to the investigational medicinal product. 
Expedited reporting of suspected unexpected serious adverse reactions related to R-AA is also 
required in line with the requirements above. 
Expedited reporting of suspected unexpected serious adverse reactions related to prednisone (and 
any other non-investigational medical products) is not required.  
7.3 
Adverse Events of Special Interest 
The following will be considered adverse events of special interest (AESI): 
• Hepatotoxicity 
• Symptomatic adrenocortical insufficiency 
• Hypertension, hypokalemia and/or edema appearing together, suggestive of 
mineralocorticoid excess 
• Hypoglycemia 
Regardless of seriousness, the Investigator shall provide detailed initial information and follow-
up using the same reporting process as for SAE reporting (see details in Section 7.2.2) within 
24 hours of awareness. 
7.4 
Overdose and dosing errors 
Special situations may require expedited reporting and/or safety evaluation. This may include: 
• Overdose of a study treatment 
• Suspected abuse/misuse of study treatment 
• Inadvertent or accidental exposure to study treatment 


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• Medication error involving study treatment 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, patient or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. Abuse corresponds to the persistent or sporadic, intentional 
excessive use of a medicinal product, which is accompanied by harmful physical or 
psychological effects. 
A study treatment overdose is the accidental or intentional use of study treatment in an amount 
higher than the dose being studied. 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded in 
the relevant sections of clinical database irrespective of whether or not associated with an 
AE/SAE.  Should a treatment error be associated with an SAE, then this would need to be 
reported to safety within 24 hours of awareness as per the guidance on SAE reporting in 
Section 7.2.2. 
 
7.5 
Pregnancy reporting 
To ensure patient safety, each pregnancy of a female partner of a male patient on study 
treatment, must be reported to Tavanta or designee within 24 hours of learning of its occurrence. 
Following consent from the female partner (non-trial participant), the pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications. 
Pregnancy must be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to Tavanta or designee using the same safety contact information as used for SAE 
reporting (see details in Section 7.2.2). Pregnancy follow-up should be recorded on the same 
form and should include an assessment of the possible relationship to the study treatment. 
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form. 
 
8 
DATA REVIEW AND DATABASE MANAGEMENT 
8.1 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Tavanta 
representative or designee will review the protocol and data capture requirements (i.e. CRFs) with 
the investigators and their staff. During the study, Tavanta employs several methods of ensuring 
protocol and Good Clinical Practice (GCP) compliance and the quality/integrity of the sites’ data. 
The field monitor will visit the site to check the completeness of patient records, the accuracy of 
data capture / data entry, the adherence to the protocol and to GCP, the progress of enrollment, 
and to ensure that study treatment is being stored, dispensed, and accounted for according to 
specifications. Continuous monitoring of each site’s data may be performed by a CRO.  
The investigator must maintain source documents for each patient in the study, consisting of case 
and visit notes (hospital or clinic medical records) containing demographic and medical 
information, and the results of any other tests or assessments. All information on CRFs must be 


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traceable to these source documents in the patient's file. The investigator must also keep the 
original informed consent form signed by the patient (a signed copy is given to the patient). 
The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or CRF entries. Tavanta monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional checks 
of the consistency of the source data with the CRFs are performed according to the study-specific 
monitoring plan. No information in source documents about the identity of the patients will be 
disclosed. 
8.2 
Data collection 
The Investigator must certify that the data entered into the CRF are complete and accurate. After 
database lock, the investigator will receive copies of the patient data for archiving at the 
investigational site. 
8.3 
Database management and quality control 
CRO/Tavanta staff will review the data entered into the CRFs by investigational staff for 
completeness and accuracy and instruct the site personnel to make any required corrections or 
additions. Queries can be asked to the investigational site. Designated investigator site staff is 
required to respond to the query and confirm or correct the data.  All queries and responses are 
subject to an audit trail. 
Concomitant medications entered into the database will be coded using the World Health 
Organization (WHO) Drug Reference List, which employs the Anatomical Therapeutic Chemical 
classification system. Concomitant procedures, non-drug therapies and AEs will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA) terminology. 
Randomization codes and data about all study drug(s) dispensed to the patient and all dosage 
changes will be tracked. Each occurrence of a code break will be reported to the clinical team and 
monitor. The code break functionality will remain available until study shut down or upon request 
of Tavanta. 
The occurrence of relevant protocol deviations will be determined. After these actions have been 
completed and the database has been declared to be complete and accurate, it will be locked, and 
the treatment codes will be made available for data analysis. 
8.4 
Data Monitoring Committee  
An independent data monitoring committee (DMC) will be established to review the safety data 
collected during the conduct of the study and monitor the progress of the study.  
Details of the composition, roles, and responsibilities, and processes of the DMC will be 
documented in a separate DMC Charter. The DMC will review safety data at specified intervals 
and can make recommendations to the Sponsor to stop or amend the study on the basis of safety 
findings. The frequency of these reviews, as well as the data to be reviewed, will be agreed with 
the DMC and outlined in the Charter, with DMC review meetings being held in a blinded manner 
to the Sponsor. Outcomes of the DMC review meetings will be shared by Tavanta or designee 
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9 
DATA ANALYSIS 
9.1 
Study design 
This is a Phase 3 randomized, open-label study to evaluate the pharmacodynamic effect of 
TAVT-45 compared to Zytiga (reference abiraterone acetate formulation, hereafter referred to as 
R-AA) in patients with mCSPC (distant metastases) and mCRPC. Randomization will be stratified 
by prostate cancer population (CSPC vs CRPC) and baseline testosterone (<10 vs ≥ 10 ng/dL). 
Patients will be treated for 84 days and randomized into one of two groups in a 1:1 ratio: 
• TAVT-45:  Administered twice daily as 1 x sachet containing TAVT-45 (250 mg abiraterone 
acetate) + Prednisone (5 mg once or twice daily, depending on prostate cancer population) 
• R-AA once daily:  Administered once daily as (2 x 500 mg Zytiga tablets) + Prednisone 
(5 mg once or twice daily, depending on prostate cancer population) 
It is planned to enroll 108 patients in this study (n=54 patients per prostate cancer population), 
randomized in a 1:1 ratio receiving either TAVT-45 (n=27 mCRPC and n=27 mCSPC patients) 
or R-AA (n=27 mCRPC and n=27 mCSPC patients). 
9.2 
Efficacy endpoints 
The primary efficacy endpoint is the comparison of the average of serum testosterone levels on 
days 9 and 10 between groups (TAVT-45 vs R-AA).  
The key secondary efficacy endpoint is the PSA-50 response, defined as a decrease of ≥ 50% in 
PSA levels from baseline at any time over the 84-day post-treatment period. 
Other secondary efficacy endpoints are as follows:  
• Serum testosterone levels at Days 28, 56 and 84 
• PSA-50 response at Days 28, 56 and 84 
• PSA levels at Days 28, 56 and 84 
• Trough concentrations of abiraterone at Days 9, 28, 56 and 84 
9.3 
Safety endpoints 
The following safety endpoints will also be assessed:  
• Incidence of treatment-emergent adverse events (TEAEs) 
• Physical examination findings  
• Clinical laboratory assessments, including potentially clinically significant changes 
• Vital signs measurements, including potentially clinically significant changes  
Safety variables will be summarized descriptively. The number and percentage of patients with 
abnormal or potentially clinically significant clinical laboratory values and vital sign 
measurements will be summarized by treatment. 
9.4 
Pharmacokinetic endpoints 
For a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK 
sampling on Day 1 and Day 9, the following PK parameters will be determined: 
• Area under the concentration-time curve from time zero to 12 hours post dose  
(AUC0-12)  
• Maximum measured plasma concentration (Cmax)  
• Minimum measured plasma concentration (Cmin)  


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• Time to maximum measured concentration (tmax)  
• Accumulation ratio (Rac) 
• Effective half-life (t½) 
9.5 
Other endpoints 
Other exploratory endpoints may be described within the study SAP.  
9.6 
Sample size 
In this study, the effects of TAVT-45 250 mg BID on serum testosterone will be compared to 
R-AA (given at 1000 mg QD) based on the equivalence approach of determining the 90% 
confidence interval (CI) of the test-to-reference geometric mean ratio within the 80 to 125% 
equivalence limit  [1,2].  
Under the assumptions of a coefficient of variation of 25%, a lower and upper limit of 80% to 
125%, and an expected test-to-reference ratio of 1.05, 108 patients in total (54 patients in TAVT-
45 and 54 patients in R-AA) will provide approximately  80% power (two one-sided t-tests at 0.05 
level) to conclude therapeutic equivalence of TAVT-45 to R-AA. 
Among the total 108 patients planned for this study, at least 54 mCRPC patients must be enrolled 
(n=27 in each treatment arm), which will provide at least 80% power for mCRPC patients. This 
sample size for each cancer population is also consistent with a similarly designed trial evaluating 
the therapeutic equivalence of R-AA and an abiraterone acetate fine particle formulation [15].  
To ensure an adequate number of patients are enrolled given the above sample size considerations, 
additional patients may be randomized to ensure that a total of 108 patients are treated up through 
Day 9 for collection of the primary efficacy endpoint data. 
9.7 
Data analysis  
This section presents a summary of the planned statistical analyses. Before database lock, a final 
Statistical Analysis Plan (SAP) will be prepared that will contain full details of all planned 
analyses.  Any deviations from the planned analyses will be described and justified in the clinical 
study report. 
9.7.1 
General analyses 
Statistical analysis will be performed on the following populations:  
• mCRPC Intent-to-treat population (CR-ITT): All randomized patients who have mCRPC 
• Intent-to-treat population (ITT): All randomized patients inclusive of both mCRPC and 
mCSPC 
• Safety population: All randomized patients who receive at least one dose of study 
medication, including those who do not complete the study.  
• Per-protocol population: All randomized patients who do not have a major protocol 
deviation that could potentially impact efficacy. 
 
All original and derived parameters as well as demographic data will be listed and described using 
summary statistics. Frequency counts (number of patients and percentages) will be made for each 
qualitative variable. Descriptive statistics (n, mean, standard deviation, median, minimum and 
maximum) will be calculated for each quantitative variable (unless otherwise stated) and will be 
presented by treatment (if applicable). 


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If not otherwise specified, ‘baseline’ refers to the last non-missing observation before study 
medication administration. All statistical tests will be two-sided and performed at the 5% level of 
significance, unless otherwise stated. 
For changes from baseline, only changes subsequent to the defined baseline will be shown in the 
listings and tabulations; in the listings any repeat/unscheduled measurements will be included in 
chronological order with the scheduled measurements, no unscheduled and/or repeated 
measurements (unless used as the baseline measurement) will be included in the tables. 
Handling of Missing and Incomplete Data 
If any baseline value is missing, the screening value will be used.  Post baseline missing values 
will be kept as missing. For efficacy data analyses, different missing data imputation methods 
may be explored to test the robustness of the primary efficacy analysis method and will be defined 
within the SAP. 
9.7.2 
Efficacy data analyses 
The primary endpoint, the average serum testosterone levels on days 9 and 10, will be analyzed 
by an analysis of variance (ANOVA) model with treatment as a factor. The test-to-reference 
geometric mean ratio effect and its 90% confidence interval (CI) of TAVT-45 to R-AA will be 
compared to 80% to 125% limit.  
The primary analysis will be performed based on the CR-ITT and repeated on the ITT and per-
protocol populations.  
Different missing data imputation approaches will be used as sensitivity analyses based on the 
intent-to-treat population and will be defined within the SAP.  
PSA-50 response at any time over the 84-day post-treatment period will be analyzed by a logistic 
model with treatment as a factor. Odds ratio, 95% CI using modified Wilson score method of 
TAVT-45 to R-AA will be presented.  
Serum testosterone levels at Days 28, 56 and 84 will be analyzed as the same manner as the 
primary endpoint. 
PSA-50 response at Days 28, 56 and 84 will be analyzed by a logistic model with treatment as a 
factor. Odds ratio, 95% CI and p-value will be presented.  
Trough concentrations of abiraterone at Days 9, 28, 56 and 84 will be summarized descriptively. 
The number of patients with trough concentrations abiraterone above and below 8.4 ng/mL at 
Days 9, 28, and 56 will also be summarized. 
Regarding subgroup analysis, both the primary and key secondary efficacy endpoints will also be 
repeated on the CSPC patients. 


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9.7.3 
Multiplicity and testing strategy  
In order to control the family-wise type I error, a sequential testing procedure will be 
implemented. The primary endpoint, the average of serum testosterone levels on days 9 and 10, 
will be tested using two one-sided t-tests at 0.05 alpha [1,2].  
If the equivalence of the average of serum testosterone levels on days 9 and 10 is achieved, then 
the key secondary endpoint (PSA-50 response, defined as a decrease of ≥50% in PSA levels from 
baseline at any time over the 84-day post-treatment period) will be tested at 0.05 alpha level.  
The primary and key secondary efficacy endpoints will be tested for mCRPC population using 
CR-ITT population first. If rejected, the same primary and key secondary efficacy endpoints will 
also be tested for the overall population using the ITT population. 
9.7.4 
Safety data analyses 
Treatment-emergent AEs (TEAEs) are defined as adverse events that started after the first dose 
of study drug (reference or test) or events present prior to the first dose of study treatment but 
increased in severity based on preferred term) will be summarized.  Non-treatment-emergent AEs 
will be presented in a listing but not summarized by treatment group. 
TEAEs will be summarized by treatment group; the number and percentage of patients having 
any AE, having an AE in each primary system organ class and having each individual AE will be 
presented.  Summaries will also be presented for AEs by severity and for study treatment related 
AEs.  If a patient reported more than one AE with the same preferred term, the AE with the 
greatest severity will be presented. If a patient reported more than one AE within the same primary 
system organ class, the patient will be counted only once with the greatest severity at the system 
organ class level, where applicable. SAEs will also be summarized.  Separate summaries will be 
provided for death, SAE, other TEAEs leading to study treatment interruption or study treatment 
discontinuation. 
The number and percentage of patients with abnormal or potentially clinically significant clinical 
laboratory values and vital sign measurements will be summarized by treatment. These thresholds 
will be pre-defined within the SAP. 
9.7.5 
Pharmacokinetic data analyses 
Plasma samples will be analyzed using a validated assay; the samples from all evaluable patients 
will be analyzed.  PK parameters for abiraterone will be calculated using a non-compartmental 
analysis. 
Patients who are dosed and who have sufficient concentration-time data to report at least one PK 
parameter will be included in the PK analysis. PK calculations will be performed using Phoenix™ 
WinNonlin® (Version 8.0 or higher, Pharsight Corporation) and/or SAS® (Version 9.4 or higher, 
SAS Institute Inc.). Additional details regarding the PK analysis will be included within the SAP. 
Abiraterone concentration-time data and PK parameters will be summarized by treatment group 
using descriptive statistics (n, mean, SD, min, median, max, and CV%).  Procedures for 
accounting for missing, unused, or spurious data, specific to the PK analyses, will be outlined 
separately in the SAP. 
9.7.6 
Other analyses 
Additional analyses, including other subgroup analyses and other exploratory analyses, will be 
described in the SAP. 


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10 
ETHICAL CONSIDERATIONS 
10.1 Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 
regulations (including European Directive 2001/20/EC), and with the ethical principles laid down 
in the Declaration of Helsinki. 
10.2 Informed consent procedures 
Eligible patients may only be included in the study after providing the approved Informed 
Consent, or, if incapable of doing so, after such consent has been provided by a legally acceptable 
representative(s) of the patient. In cases where the patient’s representative gives consent, the 
patient should be informed about the study to the extent possible given his/her understanding. If 
the patient is capable of doing so, he/she must indicate assent by personally signing and dating the 
Informed Consent document or a separate assent form. Informed Consent must be obtained before 
conducting any study-specific procedures (e.g. all of the procedures described in the protocol). 
The process of obtaining informed consent must be documented in the patient source documents. 
Tavanta will provide to investigators in a separate document a proposed Informed Consent form 
that complies with the ICH GCP guideline and regulatory requirements and is considered 
appropriate for this study. 
10.3 Responsibilities of the investigator 
Prior to study start, the investigator is required to sign a protocol signature page confirming his/her 
agreement to conduct the study in accordance with these documents and all of the instructions and 
procedures found in this protocol. 
If an inspection of the clinical site is requested by a regulatory authority, the investigator must 
inform Tavanta immediately that this request has been made. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
10.4 Publication of study protocol and results 
Tavanta assures that the key design elements of this protocol will be posted in a publicly accessible 
database such as clinicaltrials.gov. In addition, upon study completion and finalization of the study 
report the results of this trial will be either submitted for publication and/or posted in a publicly 
accessible database of clinical trial results. 
11 
PROTOCOL ADHERENCE 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances is an 
investigator allowed to collect additional data or conduct any additional procedures for any 
research related purpose involving any investigational drugs. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Tavanta, it 
cannot be implemented. All significant protocol deviations will be recorded and reported in the 
clinical study report. 


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12 
PROTOCOL AMENDMENTS 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Tavanta, Health Authorities prior to implementation. Only amendments that 
are intended to eliminate an apparent immediate hazard to patients/subjects may be implemented 
immediately provided the Health Authorities are subsequently notified by protocol amendment. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any patient included in this study, 
even if this action represents a deviation from the protocol. 
 
 


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Protocol Version 3.0 
 
 
13 
REFERENCES 
References are available upon request. 
 
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Tavanta Therapeutics, Inc. 
Protocol Version 3.0 
 
 
15. Stein CA, Levin R, Given R, Higano CS, Nemeth P, Bosch B, et al. Randomized phase 2 
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