Clinical trial NCT02946788
Conditions: Acne Vulgaris
Sponsor: BioPharmX, Inc.
Start date: 2017-03-13; Completion date: 2018-06-01
Enrollment: 20 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multi center open label study intended to provide photo documentation and time to response data for BPX-01 1 and 2% minocycline topical gel for the treatment of moderate to severe non-nodular inflammatory acne vulgarism.

Detailed description:
This was a 12-week, multi-center, open label, two-arm study. Subjects will be assigned to treatment with 1% or 2% BPX-01 gel. Subjects will apply 1g of the gel as a thin film to the entire face at least 30 minutes before bedtime each night for 12 weeks. Lesion counts, IGA, and Patient-Reported Outcomes (PGI-S and PGI-I) will be performed to assess efficacy. Photographs will be taken to document treatment effect.

Safety will be assessed with the vital signs, brief physical examination, clinical laboratory tests, cutaneous tolerance score, incidence of minocycline-induced skin hyperpigmentation, incidence of visual disturbances and/or headaches suggestive of pseudotumor cerebri, incidence of product related facial staining and collection of adverse events.

Arms: arm 1: BPX-01 1% minocycline topical gel arm 2: BPX-01 2% minocycline topical gel
Interventions: intervention 1: Minocycline
Intervention descriptions: intervention 1: BPX-01 1 or 2% topical gel will be applied to face once daily

Protocol documents:
Prot_000.pdf: 
BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
. 
Confidential and proprietary. Permission should be obtained before any reproduction. 
Page 1 of 47 
 
 
 
 
 
 
AN OPEN LABEL STUDY TO DOCUMENT THE TREATMENT 
EFFECT OF 1 AND 2% BPX-01 MINOCYCLINE TOPICAL GEL IN 
MODERATE TO SEVERE INFLAMMATORY NON-NODULAR ACNE 
VULGARIS 
 
PROTOCOL # BPX-01-C04 
 
 
VERSION 4.0 
06 July 2017 
 
Medical Monitor 
 
Sponsor: 
BioPharmX, Inc. 
1505 Adams Drive, Suite D 
Menlo Park, CA 94024, USA 
Tel: (650) 889-5020 
 
Sponsor Representative: 
AnnaMarie Daniels 
Executive Vice President 
Clinical & Regulatory Affairs 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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Confidential and proprietary. Permission should be obtained before any reproduction. 
Page 2 of 47 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................. 2 
SIGNATURE PAGE ....................................................................................................................... 6 
INVESTIGATOR SIGNATURE PAGE ........................................................................................ 7 
LIST OF ABBREVIATIONS ......................................................................................................... 9 
SUMMARY .................................................................................................................................. 10 
1 BACKGROUND ..................................................................................................................... 16 
1.1 Acne Vulgaris ................................................................................................................... 16 
1.2 BPX-01 Minocycline in Acne Vulgaris ........................................................................... 16 
1.3 Rationale for this Study .................................................................................................... 17 
2 STUDY HYPOTHESIS AND OBJECTIVE(S) ..................................................................... 18 
2.1 Hypothesis ........................................................................................................................ 18 
2.2 Objectives ......................................................................................................................... 18 
3 STUDY ENDPOINTS ............................................................................................................ 19 
3.1 Primary Endpoint ............................................................................................................. 19 
3.2 Secondary and Exploratory Endpoints ............................................................................. 19 
4 STUDY DESIGN .................................................................................................................... 20 
5 STUDY POPULATION ......................................................................................................... 21 
5.1 Inclusion Criteria .............................................................................................................. 21 
5.2 Exclusion Criteria ............................................................................................................. 22 
5.3 Discontinuations ............................................................................................................... 23 
6 TREATMENT ......................................................................................................................... 25 
6.1 Treatment Administered ................................................................................................... 25 
6.2 Study Treatment ............................................................................................................... 25 
6.2.1 Description ................................................................................................................ 25 
6.2.2 Storage Conditions .................................................................................................... 25 
6.2.3 Study Drug Dispensing and Return ........................................................................... 26 
6.2.4 Drug Accountability .................................................................................................. 26 
6.2.5 Method of Assignment to Treatment.......................................................................... 26 
6.2.6 Rationale for Selection and Timing of Doses in the Study ........................................ 26 
6.2.7 Assessment of Treatment Compliance ....................................................................... 27 
6.3 Concomitant Therapy ....................................................................................................... 27 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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6.3.1 Permitted Therapies .................................................................................................. 27 
6.3.2 Prohibited Therapies or Procedures ......................................................................... 28 
7 SCHEDULE OF EVENTS ..................................................................................................... 30 
8 STUDY ASSESSMENTS ....................................................................................................... 32 
8.1 Efficacy Assessments ....................................................................................................... 32 
8.1.1 Acne Lesion Counts ................................................................................................... 32 
8.1.2 Investigator Global Assessment (IGA) ...................................................................... 33 
8.1.3 Patient-Reported Outcomes (PROs) ......................................................................... 33 
8.1.3.1 Patient Global Impression of Severity (PGI-S) ...................................................... 33 
8.1.3.2 Patient Global Impression of Improvement (PGI-I) .............................................. 34 
8.1.4 Photographic Documentation ................................................................................... 35 
8.2 Safety Assessments .......................................................................................................... 35 
8.2.1 Vital Signs ................................................................................................................. 35 
8.2.2 Brief Physical Examination ....................................................................................... 35 
8.2.3 Clinical Laboratory Tests .......................................................................................... 35 
8.2.4 Cutaneous Tolerance Scores ..................................................................................... 36 
8.2.5 Incidence 
of 
Minocycline-Induced 
Skin  Hyperpigmentation,  Visual 
Disturbances/Headaches Suggestive of Pseudotumor Cerebri ............................................. 38 
8.2.6 Incidence of Product Related Facial Staining .......................................................... 38 
9 ADVERSE EVENTS .............................................................................................................. 39 
9.1 Adverse Events Causality ................................................................................................. 39 
9.2 Adverse Events Severity .................................................................................................. 40 
9.3 Serious Adverse Events .................................................................................................... 40 
9.3.1 SAE Reporting ........................................................................................................... 41 
9.4 Pregnancy Reporting ........................................................................................................ 41 
10 SAMPLE SIZE AND STATISTICAL METHODS ............................................................. 42 
10.1 Determination of Sample Size ........................................................................................ 42 
10.2 Statistical and Analytical Plans ...................................................................................... 42 
10.2.1 Analysis Populations ............................................................................................... 42 
10.2.2 Subject Disposition .................................................................................................. 42 
10.2.3 Efficacy Analysis ..................................................................................................... 42 
10.2.3.1 Primary Analysis .................................................................................................. 42 
10.2.3.2 Secondary and Exploratory Analyses .................................................................. 43 
10.2.3.3 Safety Analysis...................................................................................................... 43 
10.2.4 Interim Analysis ...................................................................................................... 44 
11 DATA QUALITY ASSURANCE/SITE MONITORNG ..................................................... 45 
12 DATA COLLECTION AND RETENTION......................................................................... 45 
13 CONFIDENTIALITY OF TRIAL DOCUMENTS AND SUBJECT RECORDS ............... 45 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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14 INVESTIGATOR’S FILES AND RETENTION OF DOCUMENTS ................................. 45 
15 ETHICS ................................................................................................................................. 45 
15.1 Local Regulations/Declaration of Helsinki .................................................................... 46 
15.2 Ethical Review ............................................................................................................... 46 
15.3 Informed Consent ........................................................................................................... 46 
16 PUBLICATION POLICY ..................................................................................................... 46 
17 REFERENCES ...................................................................................................................... 47 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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Page 5 of 47 
 
 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
. 
Confidential and proprietary. Permission should be obtained before any reproduction. 
Page 6 of 47 
 
SIGNATURE PAGE 
 
The signatures below constitute the approval of this protocol and the attachments, and provide 
the necessary assurances that this trial will be conducted according to local legal and regulatory 
requirements and all applicable U.S. federal regulations, and ICH guidelines. 
 
 
Sponsor Approval: 
 
 
AnnaMarie Daniels 
Executive Vice President, Clinical & 
Regulatory Affairs 
BioPharmX, Inc. 
10-Aug-2017 
 
Date (DD-MMM-YYYY 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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Confidential and proprietary. Permission should be obtained before any reproduction. 
Page 7 of 47 
 
Institution Name 
INVESTIGATOR SIGNATURE PAGE 
 
 
 
 
Investigator Name 
Signature 
Date (DD-MMM-YYYY) 
 
 
By my signature, I agree to personally supervise the conduct of this study at my study site and to 
ensure its conduct is in compliance with the protocol, informed consent, Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) procedures, instructions from BioPharmX and their 
representatives, the Declaration of Helsinki, International Conference on Harmonization (ICH) Good 
Clinical Practices Guidelines, U.S. federal regulations, and local regulations governing the conduct of 
clinical studies. 


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Protocol version 4.0 06 July 2017 
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Confidential and proprietary. Permission should be obtained before any reproduction. 
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BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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Confidential and proprietary. Permission should be obtained before any reproduction. 
Page 9 of 47 
 
LIST OF ABBREVIATIONS 
 
AE 
Adverse Event/Adverse Experience 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
-hCG 
-Human Chorionic Gonadotropin 
BMI 
Body Mass Index 
bpm 
Beats Per Minute 
BSA 
Body Surface Area 
BUN 
Blood Urea Nitrogen 
CK 
Creatinine Kinase 
CRF 
Case Report Form 
CK 
Creatine Kinase 
eCRF 
Electronic Case Report Form 
ET 
Early Termination 
FDA 
Food and Drug Administration 
FSH 
Follicle-Stimulating Hormone 
GCP 
Good Clinical Practice 
GGT 
Gamma-Glutamyl Transferase 
HCT 
Hematocrit 
HGB 
Hemoglobin 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IRB 
Institutional Review Board 
ITT 
Intent-To-Treat Population 
LDH 
Lactate Dehydrogenase 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MIC 
Minimum Inhibitory Concentration 
OTC 
Over-the-Counter 
PGI-I 
Patient Global Impression of Improvement 
PGI-S 
Patient Global Impression of Severity 
PP 
Per-Protocol Population 
PRO 
Patient-Reported Outcome 
RBC 
Red Blood Cells (count) 
REB 
Research Ethics Board 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SAP 
Statistical Analysis Plan 
SAF 
Safety Population 
TEAEs 
Treatment-Emergent Adverse Events 
WBC 
White Blood Cells (count) 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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Page 10 of 47 
 
SUMMARY 
Title: 
An Open Label Study to Document the Treatment Effect of 1 and 2% 
BPX-01 Minocycline Topical Gel in Moderate to Severe Inflammatory 
Non-nodular Acne Vulgaris (Protocol Number BPX-01-C04) 
Phase: 
2 
 
Population: 
Up to 40 male or female subjects aged between 18 and 40 years with 
moderate to severe inflammatory non-nodular acne vulgaris will be 
included in this study. 
 
Number of Sites: 
Up to 4 investigational sites will participate in this multicenter study. 
 
Study Duration:   Overall study duration is expected to be approximately 24 weeks 
(6 months). The study duration per subject is approximately 20-24 weeks 
(including 12 weeks of treatment, a screening period and the post-
treatment follow-up to assess time to recurrence). 
 
Hypothesis: 
BPX-01 improves disease condition in subjects with moderate to severe 
inflammatory non-nodular acne vulgaris. 
 
Objectives: 
 
Primary: 
• To obtain photo-documentation of the efficacy of BPX-01 minocycline 1% or 2% topical 
gel in the treatment of inflammatory non-nodular acne vulgaris 
 
Secondary: 
• To evaluate the cutaneous tolerance of BPX-01 minocycline 1% or 2% topical gel 
 
Endpoints: 
 
Primary Efficacy Endpoint: 
• Change from baseline in inflammatory lesion counts at Week 12 
Secondary Efficacy Endpoint: 
• Change from baseline in inflammatory lesion counts at Weeks 1, 2, 4, and 8 
Exploratory Efficacy Endpoints: 
• Subjects with at least a two-grade reduction in IGA at Week 12 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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• Percent change from baseline in inflammatory lesion counts at Weeks 1, 2, 4, 8, and 12 
• Absolute change and percent change from baseline in noninflammatory lesion counts at 
Weeks 1, 2, 4, 8, and 12 
• Absolute change and percent change from baseline in total lesion counts at Weeks 1, 2, 4, 
8, and 12 
• Absolute change and percent change from baseline in the Investigator’s Global Assessment 
(IGA) at Weeks 1, 2, 4, 8, and 12 
• Proportion of subjects with an IGA of clear (0) or almost clear (1) at Weeks 1, 2, 4, 8, and 
12 
• Proportion of subjects with at least a two-grade reduction in IGA at Weeks 2, 4, and 8 
• Change from baseline in Patient Global Impression of Severity (PGI-S) at Weeks 1, 2, 4, 8, 
and 12 
• Patient Global Impression of Improvement (PGI-I) at Weeks 1, 2, 4, 8, and 12 
Safety Endpoints: 
• Incidence of treatment-emergent adverse events (TEAEs) 
• Shift from baseline in clinical hematology and chemistry laboratory tests 
• Change from baseline in the cutaneous tolerance score evaluated by the observer 
(erythema, scaling-peeling, edema) 
• Change from baseline in the cutaneous tolerance score evaluated by the subject (tightness, 
burning, stinging, itching) 
• Incidence of visual disturbances/headaches suggestive of pseudotumor cerebri and 
minocycline-induced skin hyperpigmentation 
• Incidence of product related facial staining 
 
Overall Study Design: 
 
This is a 12-week, multi-center, open label, two-arm study. 
 
Subjects will be assigned to treatment with 1% or 2% BPX-01 gel. Subjects will apply 1g of the 
gel as a thin film to the entire face at least 30 minutes before bedtime each night for 12 weeks. 
Lesion counts, IGA, and Patient-Reported Outcomes (PGI-S and PGI-I) will be performed to 
assess efficacy. Photographs will be taken to document treatment effect. 
 
Safety will be assessed with the vital signs, brief physical examination, clinical laboratory tests, 
cutaneous tolerance score, incidence of minocycline-induced skin hyperpigmentation, incidence 
of visual disturbances and/or headaches suggestive of pseudotumor cerebri, incidence of product 
related facial staining and collection of adverse events. 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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Confidential and proprietary. Permission should be obtained before any reproduction. 
Page 12 of 47 
 
Inclusion Criteria: 
 
Subjects will be eligible if they meet all of the following criteria at the screening and baseline 
(Day 0) visits, unless specified otherwise: 
 
1. Male or female subjects aged between 18 and 40 years of age, inclusive, at the time of 
consent. 
2. Subjects do not have any medical conditions, other than acne vulgaris, that in the opinion 
of the investigator, put the subject at unacceptable risk or could interfere with study 
assessments or integrity of the data. 
3. Moderate to severe inflammatory non-nodular acne vulgaris, defined as follows: 
a. IGA score of 3 (moderate) or 4 (severe) at baseline (Day 0); 
b. 20-60 inflammatory lesions on the face at baseline (Day 0); 
c. 0-100 noninflammatory lesions on the face at baseline (Day 0); 
d. Maximum of 2 nodules (≥ 5 mm) on the face at baseline (Day 0). 
4. Female subjects of childbearing potential (including pre-puberty) are willing to use 
effective contraceptive method for at least 28 days before baseline (Day 0) and at least 
28 days after the last study product administration or have a sterilized or same-sex partner 
for the duration of the study. Effective contraceptive methods are: systemic hormonal 
contraceptives, intrauterine device or barrier method of contraception in conjunction with 
spermicide, or agree to sexual abstinence. Hormonal contraceptives must be on a stable 
dose for at least 12 weeks before baseline (Day 0). Subjects using low dose oral 
contraceptives must use a second form of birth control (e.g., barrier method such as 
condoms with spermicide). 
Note: Female subjects of nonchildbearing potential are defined as follows: 
a. Female subjects who have had surgical sterilization (hysterectomy, bilateral 
oophorectomy, bilateral salpingectomy, or bilateral tubal ligation); 
b. Female subjects who have had a cessation of menses for at least 12 months and a 
follicle-stimulating hormone (FSH) test confirming nonchildbearing potential 
(refer to the central laboratory reference range for menopausal women) or 
cessation of menses for at least 24 months without FSH levels confirmed; 
5. Female subjects of childbearing potential must have a negative urine pregnancy test at 
screening and baseline (Day 0). 
6. Treatment with hormonal therapy must be on a stable dose and frequency for at least 
12 weeks before baseline (Day 0) and must remain stable throughout the study. 
7. Subjects who use make-up, facial moisturizers, creams, lotions, cleansers and/or 
sunscreens must have used the same product brands/types for a minimum period of 14 
days prior to baseline (Day 0), must agree not to change brand/type or frequency of use 
throughout the study and must agree not to use make-up, facial moisturizers, creams, 
lotions, cleansers and/or sunscreens on the clinic visit days before the visit. 
8. Subjects must be capable of giving informed consent and the written informed consent 
must be obtained prior to any study-related procedures. 
 
Exclusion Criteria: 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
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Page 13 of 47 
 
Subjects will not be eligible if they meet any of the following criteria at the screening or baseline 
(Day 0) unless specified otherwise: 
 
1. Female subject who is breastfeeding, pregnant or who is planning a pregnancy during the 
study. 
2. Have acne fulminans or conglobata, or nodulocystic acne. 
3. Have a history of skin disease, presence of skin condition, skin pigmentation or excessive 
facial hair that, in the opinion of the investigator, would interfere with the study. 
4. Have a history of cancer or lymphoproliferative disease other than a successfully treated 
non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized 
carcinoma in situ of the cervix. 
5. Have had any prior treatment with minocycline. 
6. Presence of visual disturbances and/or headaches suggestive of pseudotumor cerebri at 
screening or baseline (Day 0). 
7. Have a clinical chemistry or hematology laboratory value that is abnormal at the 
screening visit and that is considered clinically significant by the investigator. 
8. Has an ALT or AST at screening greater than or equal to 2 times the upper limit of 
normal. 
9. Have used on the face an over-the-counter (OTC) topical medication for the treatment of 
acne vulgaris including benzoyl peroxide, topical anti-inflammatory medications, 
corticosteroids, salicylic acid, α-hydroxy/glycolic, antibacterial/antiseptic soap or wash 
within 14 days prior to baseline (Day 0). Topical acne treatments that do not have 
significant or measurable systemic absorption (e.g., benzoyl peroxide, salicylic acid) are 
allowed for treatment of acne on the back, shoulders and chest only. 
10. Have used prescription topical retinoid (e.g. tretinoin, tazarotene, adapalene) or 
antimicrobials (e.g. clindamycin, erythromycin) or other prescription topical medications 
for the treatment of acne vulgaris within 28 days of baseline (Day 0). Topical antibiotics 
(not containing minocycline or other tetracycline-class antibiotics) may be used to treat 
non-acne skin lesions outside the face. 
11. Have used systemic antibiotics or other systemic anti-acne drugs not mentioned in the 
exclusion criteria within 28 days of baseline (Day 0). 
12. Have used oral, intranasal, or injectable corticosteroids within 28 days of baseline (Day 
0) or require them during the study. Inhaled corticosteroids for stable medical conditions 
are allowed. 
13. Have received an investigational therapy (including investigational drug or procedure) 
within 28 days of baseline (Day 0) or plan to use one during the study. 
14. Have had a facial procedure (e.g. chemical peel, laser, microdermabrasion) within 8 
weeks of baseline (Day 0). 
15. Have excessive sun exposure, is planning a trip to a sunny climate or used tanning booths 
within 28 days prior to baseline (Day 0) or is not willing to minimize natural and artificial 
sunlight exposure during the study. Use of sunscreen products and protective apparel are 
recommended when exposure cannot be avoided. 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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Page 14 of 47 
 
16. Have received photodynamic therapy or phototherapy with blue or red light within 12 
weeks of baseline (Day 0). 
17. Have used androgen receptor blockers (such as spironolactone or flutamide) within 12 
weeks of baseline (Day 0). 
18. Have used drospirenone, chlormadinone acetate, and cyproterone acetate within 26 weeks 
of baseline (Day 0). 
19. Have used oral retinoid (e.g., isotretinoin) within 52 weeks prior to baseline (Day 0) or 
vitamin A supplements greater than 10,000 U/d within 26 weeks of baseline (Day 0). 
20. History of clinically significant drug or alcohol abuse in the last year prior to baseline 
(Day 0) as judged by the investigator. 
21. Has known or suspected allergy to minocycline, tetracycline-class antibiotics or any 
component of the investigational product. 
 
Statistical Analysis: 
 
No statistical analysis will be performed for this small study. The low sample size will provide 
directional data only and no statistical significance between or within treatment groups is 
expected. 


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Page 15 of 47 
 
 


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Protocol version 4.0 06 July 2017 
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Page 16 of 47 
 
1 
BACKGROUND 
1.1 
Acne Vulgaris 
Acne vulgaris is the most prevalent skin disorder and it affects approximately 85% of the 
population at some time between the age of 12 and 24 years, and it frequently persists into 
adulthood.1,2 Acne is a multifactorial chronic disease and different factors contribute to its 
development such as: (1) sebaceous gland hyperactivity with seborrhea, (2) abnormal 
keratinocyte desquamation, and (3) bacterial colonization and proliferation responsible for local 
inflammatory changes.3,4 Clinically, acne is characterized by two major types of lesions that are 
typically located on the face, chest, and back: (1) noninflammatory open and closed comedones 
and (2) inflammatory papules, pustules and nodules. During puberty, surges in androgen cause 
over production of sebum along with abnormal desquamation of the epidermal lining of hair 
follicles. Formed by sebum and skin debris, the comedones provide an ideal environment for the 
proliferation of Propionibacterium acnes bacteria which are then responsible for triggering local 
inflammatory reactions by releasing inflammatory mediators. A wide variety of drug products, 
topical and systemic, are available to treat acne. The most effective acne therapies work by 
targeting the sebaceous gland and decreasing sebum production. 
 
Because of their known anti-inflammatory properties, minocycline products have been 
particularly successful in the treatment of moderate to severe inflammatory acne vulgaris. 
However, there have been severe side effects associated with the oral dosage forms of 
minocycline. There is currently no commercially available topical dosage form of minocycline. 
 
1.2 
BPX-01 Minocycline in Acne Vulgaris 
BPX-01 is a topical gel comprising minocycline hydrochloride (HCl) as the drug substance. It is 
a hydrophilic formulation that relies on full dissolution of the drug substance to ensure efficient 
and targeted delivery to the facial skin. In preclinical studies, uptake of BPX-01 has been 
confirmed to reach the epidermis and pilosebaceous units, with local levels above the minimum 
inhibitory concentration (MIC) value for P. acnes.5 
 
Minocycline is an antibiotic currently available in multiple oral dosage forms for treating various 
bacterial infections. Minocycline inhibits the growth of certain species of bacteria through 
inhibition of protein synthesis by blocking aminoacyl-tRNA binding to the mRNA-ribosome 
complex. Minocycline is active against a number of gram-positive and gram-negative organisms, 
including P. acnes. The mechanism through which minocycline ameliorates acne is not fully 
elucidated, although reducing the bacterial count may reduce the size and quantity of lesions by 
reducing inflammation.6,7,8 
 
BPX-01, 1% gel is intended for use in the treatment of non-nodular, moderate to severe 
inflammatory acne vulgaris in patients 9 years of age and older. There has been one clinical 
study (Phase 2a) completed with BPX-01 1% minocycline topical gel and another dose finding 
study (Phase 2b) completed with BPX-01 1% and 2% minocycline topical gel. 


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Page 17 of 47 
 
1.3 
Rationale for this Study 
BioPharmX is developing a new therapeutic option for patients with moderate to severe acne 
vulgaris. Because of an anticipated lower systemic exposure and extended half-life with BPX-01, 
the potential for many of the side effects seen with oral Solodyn or other oral minocycline 
formulations are expected to be markedly minimized or completely abrogated. The objective of 
this study is to document the treatment effect of 1 and 2% topical minocycline gel in subjects 
with moderate to severe inflammatory non-nodular acne vulgaris. 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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Page 18 of 47 
 
2 
STUDY HYPOTHESIS AND OBJECTIVE(S) 
2.1 
Hypothesis 
BPX-01 improves disease condition in subjects with moderate to severe inflammatory non-
nodular acne vulgaris. 
 
2.2 
Objectives 
Primary: 
• To obtain photo-documentation of the efficacy of BPX-01 minocycline 1% or 2% topical 
gel in the treatment of inflammatory non-nodular acne vulgaris 
Secondary: 
• To evaluate the cutaneous tolerance of BPX-01 minocycline 1% or 2% topical gel 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
Protocol version 4.0 06 July 2017 
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3 
STUDY ENDPOINTS 
3.1 
Primary Endpoint 
• Change from baseline in inflammatory lesion counts at Week 12 
 
3.2 
Secondary and Exploratory Endpoints 
Secondary Efficacy Endpoint: 
• Change from baseline in inflammatory lesion counts at Weeks 1, 2, 4, and 8 
Exploratory Efficacy Endpoints: 
• Subjects with at least a two-grade reduction in IGA at Week 12 
• Percent change from baseline in inflammatory lesion counts at Weeks 1, 2, 4, 8, and 12 
• Absolute change and percent change from baseline in noninflammatory lesion counts at 
Weeks 1, 2, 4, 8, and 12 
• Absolute change and percent change from baseline in total lesion counts at Weeks 1, 2, 4, 
8, and 12 
• Absolute change and percent change from baseline in the Investigator’s Global Assessment 
(IGA) at Weeks 1, 2, 4, 8, and 12 
• Proportion of subjects with an IGA of clear (0) or almost clear (1) at Weeks 1, 2, 4, 8, and 
12 
• Proportion of subjects with at least a two-grade reduction in IGA at Weeks 1, 2, 4, and 8 
• Change from baseline in Patient Global Impression of Severity (PGI-S) at Weeks 1, 2, 4, 8, 
and 12 
• Patient Global Impression of Improvement (PGI-I) at Weeks 1, 2, 4, 8, and 12 
Safety Endpoints: 
• Incidence of treatment-emergent adverse events (TEAEs) 
• Shift from baseline in clinical hematology and chemistry laboratory tests 
• Change from baseline in the cutaneous tolerance score evaluated by the observer 
(erythema, scaling-peeling, edema) 
• Change from baseline in the cutaneous tolerance score evaluated by the subject (tightness, 
burning, stinging, itching) 
• Incidence of visual disturbances/headaches suggestive of pseudotumor cerebri and 
minocycline-induced skin hyperpigmentation 
• Incidence of product related facial staining 


BioPharmX– Protocol BPX-01-C04- BPX-01 Minocycline in Acne Vulgaris 
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4 
STUDY DESIGN 
This is a 12-week, multi-center, open label, two-arm study. 
 
Subjects will be assigned to treatment with 1% or 2 % BPX-01 gel. Subjects will apply 1g of the 
gel as a thin film to the entire face at least 30 minutes before bedtime each night for 12 weeks. 
Lesion counts, IGA, and Patient-Reported Outcomes (PGI-S and PGI-I) will be performed to 
assess efficacy. Photographs will be taken to document treatment effect. 
 
Safety will be assessed with the vital signs, brief physical examination, clinical laboratory tests, 
cutaneous tolerance score, incidence of minocycline-induced skin hyperpigmentation, incidence 
of visual disturbances and/or headaches suggestive of pseudotumor cerebri, incidence of product 
related facial staining and collection of adverse events. 


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5 
STUDY POPULATION 
This study will include up to 40 subjects with moderate to severe inflammatory non-nodular acne 
vulgaris, defined as IGA score of 3 (moderate) or 4 (severe), 20-60 inflammatory lesions, 0-100 
noninflammatory lesions and a maximum of 2 nodules on the face at baseline. Subjects will be 
male or female, aged between 18 and 40 years. Subjects who discontinue after taking the first 
dose of study drug will not be replaced. 
 
5.1 
Inclusion Criteria 
Subjects will be eligible if they meet all of the following criteria at the screening and baseline 
(Day 0) visits, unless specified otherwise: 
 
1. Male or female subjects aged between 18 and 40 years of age, inclusive, at the time of 
consent. 
2. Subjects do not have any medical conditions, other than acne vulgaris, that in the opinion 
of the investigator, put the subject at unacceptable risk or could interfere with study 
assessments or integrity of the data. 
3. Moderate to severe inflammatory non-nodular acne vulgaris, defined as follows: 
a. IGA score of 3 (moderate) or 4 (severe) at baseline (Day 0); 
b. 20-60 inflammatory lesions on the face at baseline (Day 0); 
c. 0-100 noninflammatory lesions on the face at baseline (Day 0); 
d. Maximum of 2 nodules (≥ 5 mm) on the face at baseline (Day 0). 
4. Female subjects of childbearing potential (including pre-puberty) are willing to use 
effective contraceptive method for at least 28 days before baseline (Day 0) and at least 
28 days after the last study product administration or have a sterilized or same-sex partner 
for the duration of the study. Effective contraceptive methods are: systemic hormonal 
contraceptives, intrauterine device or barrier method of contraception in conjunction with 
spermicide, or agree to sexual abstinence. Hormonal contraceptives must be on a stable 
dose for at least 12 weeks before baseline (Day 0). Subjects using low dose oral 
contraceptives must use a second form of birth control (e.g., barrier method such as 
condoms with spermicide). 
Note: Female subjects of nonchildbearing potential are defined as follows: 
a. Female subjects who have had surgical sterilization (hysterectomy, bilateral 
oophorectomy, bilateral salpingectomy, or bilateral tubal ligation); 
b. Female subjects who have had a cessation of menses for at least 12 months and a 
follicle-stimulating hormone (FSH) test confirming nonchildbearing potential 
(refer to the central laboratory reference range for menopausal women) or 
cessation of menses for at least 24 months without FSH levels confirmed; 
5. Female subjects of childbearing potential must have a negative urine pregnancy test at 
screening and baseline (Day 0). 
6. Treatment with hormonal therapy must be on a stable dose and frequency for at least 
12 weeks before baseline (Day 0) and must remain stable throughout the study. 


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7. Subjects who use make-up, facial moisturizers, creams, lotions, cleansers and/or 
sunscreens must have used the same product brands/types for a minimum period of 14 
days prior to baseline (Day 0), must agree not to change brand/type or frequency of use 
throughout the study and must agree not to use make-up, facial moisturizers, creams, 
lotions, cleansers and/or sunscreens on the clinic visit days before the visit. 
8. Subjects must be capable of giving informed consent and the written informed consent 
must be obtained prior to any study-related procedures. Subject under 18 years of age 
must sign an assent form, and their parent(s) or legal representative must have read and 
signed the informed consent form prior to any study-related procedures. 
 
5.2 
Exclusion Criteria 
Subjects will not be eligible if they meet any of the following criteria at the screening or baseline 
(Day 0) unless specified otherwise: 
 
1. Female subject who is breastfeeding, pregnant or who is planning a pregnancy during the 
study. 
2. Have acne fulminans or conglobata, or nodulocystic acne. 
3. Have a history of skin disease, presence of skin condition, skin pigmentation or excessive 
facial hair that, in the opinion of the investigator, would interfere with the study. 
4. Have a history of cancer or lymphoproliferative disease other than a successfully treated 
non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized 
carcinoma in situ of the cervix. 
5. Have had any prior treatment with minocycline. 
6. Presence of visual disturbances and/or headaches suggestive of pseudotumor cerebri at 
screening or baseline (Day 0). 
7. Have a clinical chemistry or hematology laboratory value that is abnormal at the 
screening visit and that is considered clinically significant by the investigator. 
8. Has an ALT or AST at screening greater than or equal to 2 times the upper limit of 
normal. 
9. Have used on the face an over-the-counter (OTC) topical medication for the treatment of 
acne vulgaris including benzoyl peroxide, topical anti-inflammatory medications, 
corticosteroids, salicylic acid, α-hydroxy/glycolic, antibacterial/antiseptic soap or wash 
within 14 days prior to baseline (Day 0). Topical acne treatments that do not have 
significant or measurable systemic absorption (e.g., benzoyl peroxide, salicylic acid) are 
allowed for treatment of acne on the back, shoulders and chest only. 
10. Have used prescription topical retinoid (e.g. tretinoin, tazarotene, adapalene) or 
antimicrobials (e.g. clindamycin, erythromycin) or other prescription topical medications 
for the treatment of acne vulgaris within 28 days of baseline (Day 0). Topical antibiotics 
(not containing minocycline or other tetracycline-class antibiotics) may be used to treat 
non-acne skin lesions outside the face. 
11. Have used systemic antibiotics or other systemic anti-acne drugs not mentioned in the 
exclusion criteria within 28 days of baseline (Day 0). 


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12. Have used oral, intranasal, or injectable corticosteroids within 28 days of baseline (Day 
0) or require them during the study. Inhaled corticosteroids for stable medical conditions 
are allowed. 
13. Have received an investigational therapy (including investigational drug or procedure) 
within 28 days of baseline (Day 0) or plan to use one during the study. 
14. Have had a facial procedure (e.g. chemical peel, laser, microdermabrasion) within 8 
weeks of baseline (Day 0). 
15. Have excessive sun exposure, is planning a trip to a sunny climate or used tanning booths 
within 28 days prior to baseline (Day 0) or is not willing to minimize natural and artificial 
sunlight exposure during the study. Use of sunscreen products and protective apparel are 
recommended when exposure cannot be avoided. 
16. Have received photodynamic therapy or phototherapy with blue or red light within 12 
weeks of baseline (Day 0). 
17. Have used androgen receptor blockers (such as spironolactone or flutamide) within 12 
weeks of baseline (Day 0). 
18. Have used drospirenone, chlormadinone acetate, and cyproterone acetate within 26 weeks 
of baseline (Day 0). 
19. Have used oral retinoid (e.g., isotretinoin) within 52 weeks prior to baseline (Day 0) or 
vitamin A supplements greater than 10,000 U/d within 26 weeks of baseline (Day 0). 
20. History of clinically significant drug or alcohol abuse in the last year prior to baseline 
(Day 0) as judged by the investigator. 
21. Has known or suspected allergy to minocycline, tetracycline-class antibiotics or any 
component of the investigational product. 
 
5.3 
Discontinuations 
Subjects have the right to withdraw from the study at any time for any reason without penalty. 
The investigator also has the right to withdraw subjects from the study if he/she feels it is in the 
best interest of the subject or if the subject is uncooperative or noncompliant. Should a subject 
decide to withdraw, all efforts will be made to complete and report the observations as 
thoroughly as possible, particularly the follow-up examination. 
 
The investigator or one of his or her staff members should contact the subject either by telephone 
or through a personal visit to determine as completely as possible the reason for the withdrawal. 
A complete final evaluation at the time the subject’s withdrawal should be made with an 
explanation of why the subject is withdrawing from the study. If the reason for removal of a 
subject is an adverse event or an abnormal laboratory test result, the principal specific event or 
test will be recorded. The criteria for enrollment must be followed explicitly. Subjects who 
discontinue the study after taking his or her first dose, but before the Week 12 visit will be asked, 
if they agree, to come for the last assessments listed at Week 12 (exit visit). Subjects who 
discontinue will not be replaced. 
 
Reasons for discontinuation include the following: 
• 
The investigator decides that the subject should be withdrawn. If this decision is made 


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Page 24 of 47 
 
because of a serious adverse event, the study drug is to be discontinued and appropriate 
measures are to be taken. The investigator will notify the sponsor immediately. 
• 
The attending physician requests that the subject be withdrawn from the study. 
• 
The subject for any reason requires treatment with another therapeutic agent that has been 
demonstrated to be effective for treatment of the study indication. In this case, 
discontinuation from the study occurs immediately upon introduction of the new agent. 
• 
The subject is lost to follow-up. In this case, a reasonable attempt to contact the subject and 
ascertain his or her status must be made, and these attempts must be documented. 
• 
The sponsor or regulatory authorities, for any reason, stop the study. All subjects will be 
discontinued from the study and notified of the reasons for the discontinuation. 
• 
Pregnancy occurs at any time during the study. 
• 
Presence of clinically significant symptoms suggestive of pseudotumor cerebri. 
• 
Other: the subject may withdraw from the study for any other reason, including withdrawal 
of consent. 


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Page 25 of 47 
 
6 
TREATMENT 
6.1 
Treatment Administered 
Subjects who fulfill all of the inclusion criteria and none of the exclusion criteria will be 
accepted into the study. Each subject should read and sign an informed consent form prior to any 
screening procedures being performed. This study involves a comparison of 1% and 2% BPX-01 
administered topically on a clean face at least 30 minutes before bedtime each night for a total 
duration of 12 weeks. Subjects will be assigned sequentially to either 1 or 2% BPX-01 in a 1:1 
ratio on Day 0 (baseline) as follows: 
 
1st 10 subjects: BPX-01 1%, 1 g topical gel once a day for 12 weeks 
2nd 10 subjects: BPX-01 2%, 1 g topical gel once a day for 12 weeks 
Subjects should complete their cleansing routine (e.g., washing face, bathe, shower, shaving) and 
have a clean face prior to study drug application and should not apply anything else to their face 
afterward in the evening. Every effort should be made to keep the same skin care habits 
throughout the study. 
 
If an application is missed, subjects should apply the study product as soon as they remember on 
the same day. However, if it is the next day, the missed dose should be skipped and the next dose 
taken as normal. No double dose should be taken for any reason. 
 
6.2 
Study Treatment 
 
6.2.1 Description 
 
BPX-01 (1% and 2%) is formulated as a topical gel comprising minocycline HCl as the drug 
substance. The gel will be provided by BioPharmX in single-dose, aluminum tubes lined with an 
inert, biocompatible material. Each tube will contain 1.5 g of gel, calculated to deliver 1 g of 
drug product. 
 
The investigator will be responsible for drug accountability. After verification of the drug 
accountability by the sponsor or designee, all study product (used and unused tubes) will be 
returned to the sponsor or designee after the study completion. 
 
6.2.2 Storage Conditions 
 
The study drug will be provided by BioPharmX to the investigator. It will be kept, on site, in a 
secure, temperature-controlled place at 15°C to 30°C with protection from moisture. It will only 
be supplied to subjects in the trial under the supervision of the investigator. Room temperature on 
site will be monitored and recorded. The packaging of investigational product for this clinical 


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study has been designed with these conditions in mind and precautions other than limiting 
temperature range are not required. 
 
6.2.3 Study Drug Dispensing and Return 
 
The study drug will be applied at home throughout the study, except for the first dose that will be 
applied on site at the baseline (Day 0) visit under the supervision of the study staff. 
 
The study drug will be dispensed in a medication kit by the study site to the subjects and will be 
given with subject instructions for application. At baseline (Day 0) and Week 2 visits, subjects 
will receive one medication kit containing 18 tubes each. At Week 4 and Week 8 visits, subjects 
will receive two kits for a total of 36 tubes each. Single-use tubes of 1.5 g (for delivery of 1 g of 
gel) will be given and 1 g of gel is to be applied on the entire face once daily. Subjects are to 
return all tubes (used and unused) to the study site at the Week 1, 2, 4, 8, and 12 visits. The 
number of tubes will be counted prior to dispensing and upon return and the counts will be 
recorded in the source documents and eCRF. Each subject will be instructed on the importance of 
returning study drug at the specified visits. If a subject does not return study drug, he or she will 
be instructed to return it as soon as possible. 
 
6.2.4 Drug Accountability 
 
The investigator is responsible for maintaining accurate records of the study drug received 
initially, the study drug dispensed/used/returned by subjects and the study drug destroyed or 
returned to the sponsor or designee. All study drug accountability forms and treatment logs must 
be retained in the Investigator’s study file. These records must be available for inspection at any 
time by the sponsor, its designees or by regulatory agencies. 
 
6.2.5 Method of Assignment to Treatment 
 
Up to 40 subjects will be assigned sequentially (1:1) to one of the two treatment groups. 
 
6.2.6 Rationale for Selection and Timing of Doses in the Study 
 
In preclinical studies, different BPX-01 formulations (1% and 4%) were applied as mg/cm2 to 
cover approximately 5% to 15% of body surface area (BSA). Topical administration of BPX-01 
once daily demonstrated rapid absorption in rats at all doses. The amount of BPX-01 1% 
minocycline detected in rats at the 2.5 mg/cm2/d dose group represents the maximum amount of 
absorption, because rat skin is thinner than human skin. No systemic uptake of minocycline was 
seen in the low dose group in minipigs. The lack of minocycline in plasma with delivery of 
BPX-01 1% minocycline in minipigs at 2.5 mg/cm2/d is very promising because it supports the 
hypothesis that targeted delivery of minocycline to the skin with limited systemic exposure is 
possible.5 
 
The uptake of minocycline in minipig skin shows levels above the MIC value for P. acnes, 
which was found to be 0.035 µg/mL. Therefore, on the basis of these results, BPX-01 1% 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
Page 27 of 47 
 
minocycline at 2.5 mg/cm2/day is the proposed first-in-human clinical dose (1 g of BPX-01, 1% 
minocycline applied as a thin film to the entire face) that was used in a Phase 2a study.5 In a 
currently ongoing 2b dose finding study, the 1% and 2% doses are being evaluated to establish 
the lowest effective dose. This current open label study will provide early data on the correlation 
between IGA, lesion counts and photo-documentation. 
 
6.2.7 Assessment of Treatment Compliance 
 
Compliance to treatment with BPX-01 minocycline 1% or 2% will be monitored at each visit. 
Compliance to treatment will be assessed by direct questioning, review of the subject’s diary, 
and by maintaining adequate drug dispensing and return records. The tubes containing study 
drug will be collected from each subject at the Week 1, 2, 4, 8, and 12 visits to further assess 
treatment compliance. Any deviation from the prescribed dosage regimen will be recorded in the 
source document and CRF. 
 
Subjects who are significantly noncompliant to treatment will be counseled and could be 
discontinued from the study, at the discretion of the investigator following consultation with the 
sponsor. Similarly, a subject will be considered significantly noncompliant if he or she 
intentionally or repeatedly takes more than the prescribed amount of medication in the same time 
frame as judged by the investigator. 
 
6.3 
Concomitant Therapy 
All medications (including OTC drugs, vitamins, and antacids) taken less than or equal to 28 
days prior to screening and throughout the study must be recorded. 
 
The investigator should assess for acceptability any concomitant procedures, medications, and 
dietary supplements that are not explicitly prohibited. 
 
Medication entries may be captured as generic or trade names. Trade names should be used for 
combination drugs. Entries should include as much as possible of the following information: the 
dose, unit, frequency of administration, route of administration, start date, discontinuation date, 
and indication. If the medication is discontinued or the dosage changed, these details must be 
recorded. 
 
6.3.1 Permitted Therapies 
 
The following therapies are permitted: 
• Topical acne treatments that do not have significant or measurable systemic absorption (e.g. 
benzoyl peroxide, salicylic acid) are allowed for treatment of acne on the back, shoulders and 
chest only; 
• Topical antibiotics (not containing minocycline or other tetracycline-class antibiotics) may be 
used to treat non-acne skin lesions outside the face; 


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Page 28 of 47 
 
• Inhaled corticosteroids for stable medical conditions are allowed; 
• Hormonal therapies (including oral contraceptives) are allowed but must be on stable dose 
and frequency for at least 12 weeks before baseline (Day 0) and must remain stable 
throughout the study (see inclusion criteria, Section 5.1, for more details); 
• Subjects will be instructed that the use of make-up, facial moisturizers, creams, lotions, 
cleansers and/or sunscreens are permitted but they must use the same brands/types for a 
minimum period of 14 days prior to baseline (Day 0) and must agree not to change 
brand/type or frequency of use throughout the study. Subjects must also agree not to use 
make-up, facial moisturizers, creams, lotions, cleansers and/or sunscreens on the clinic visit 
days before the visit; 
• Subjects who choose to use make-up, facial moisturizers, creams, lotions, cleansers and/or 
sunscreens should try to use non-comedogenic products. 
 
6.3.2 Prohibited Therapies or Procedures 
 
The following therapies are prohibited: 
• The use of any OTC topical medications for the treatment of acne vulgaris on the face 
including benzoyl peroxide, topical anti-inflammatory medications, corticosteroids, salicylic 
acid, α-hydroxy/glycolic, antibacterial/antiseptic soap or wash within 14 days prior to 
baseline (Day 0) and throughout the study; 
• The use of any prescription topical retinoid (e.g. tretinoin, tazarotene, adapalene) or 
antimicrobials (e.g. clindamycin, erythromycin) or any other prescription topical medications 
for the treatment of acne vulgaris within 28 days of baseline (Day 0) and throughout the 
study (except topical antibiotics for non-acne skin lesions as indicated in Section 6.3.1); 
• The use of systemic antibiotics or other systemic anti-acne drugs not mentioned in the 
exclusion criteria (Section 5.2) within 28 days of baseline (Day 0) and throughout the study; 
• The use of oral, intranasal, or injectable corticosteroids within 28 days of baseline (Day 0) 
and throughout the study; 
• The use of androgen receptor blockers (e.g., spironolactone, flutamide) within 12 weeks of 
baseline (Day 0) and throughout the study; 
• The use of an oral retinoid (e.g., isotretinoin) within 52 weeks prior to baseline (Day 0) or 
vitamin A supplements greater than 10,000 U/d within 26 weeks of baseline (Day 0) and 
throughout the study; 
• Facial procedures (e.g. chemical peel, laser, microdermabrasion) within 8 weeks of baseline 
(Day 0) and throughout the study; 
• Photodynamic therapy or phototherapy with blue or red light within 12 weeks of baseline 
(Day 0) and throughout the study; 
• The use of drospirenone, chlormadinone acetate, and cyproterone acetate within 26 weeks of 
baseline (Day 0) and throughout the study; 


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• The use of another investigational therapy within 28 days of baseline (Day 0) and throughout 
the study. 


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7 
SCHEDULE OF EVENTS 
Screening evaluation will only be performed after the subject has agreed to participate and has 
signed and dated the informed consent form. No treatment or trial-related procedures will be 
initiated before the informed consent is signed. The baseline (Day 0) visit must be performed, at 
the latest, 30 days after the screening visit. 
 
Screening evaluation will be performed according to inclusion and exclusion criteria. If the 
individual fulfills all inclusion criteria and no exclusion criteria, he or she may be included in the 
study. 
 
Table 1 provides a description of the procedures to be performed at each visit. 
 
Table 1 : Schedule of Events 
 
Procedures/ Time 
Points: 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Screening 
Baseline / 
Day 0 
Week 1 
Week 2 
Week 4 
Week 8 
Week 12 
TBD5 
Recurrence 
Visit windows 
–30 to –1 d 
±3 d 
±3 d 
±3 d 
± 3 d 
±3 d 
n/a 
Informed consent, 
medical history and 
HIPAA 
X 
Demographics 
X 
Collect/Record 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Eligibility Assessment 
X 
X 
Brief Physical 
examination 
X 
X 
Vital signs1 
X 
X 
Basic Chemistry and 
Hematology 
Laboratory Panel2 
X 
X 
Urine Pregnancy Test3 
X 
X 
X 
Patient global 
impression of severity 
(PGI-S) 
X 
X 
X 
X 
X 
X 
X 
Patient global 
impression of 
improvement (PGI-I) 
X 
X 
X 
X 
X 
X 
Investigator Global 
Assessment (IGA) 
X 
X 
X 
X 
X 
X 
X 
X 
Lesion Counts 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator Cutaneous 
Tolerance Scores4 
X 
X 
X 
X 
X 
X 


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Procedures/ Time 
Points: 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Screening 
Baseline / 
Day 0 
Week 1 
Week 2 
Week 4 
Week 8 
Week 12 
TBD5 
Recurrence 
Visit windows 
–30 to –1 d 
±3 d 
±3 d 
±3 d 
± 3 d 
±3 d 
n/a 
Subject Cutaneous 
Tolerance Scores4 
X 
X 
X 
X 
X 
X 
Presence or absence of 
visual 
disturbances/headache 
s suggestive of 
pseudotumor cerebri 
X 
X 
X 
X 
X 
Presence or absence of 
minocycline-induced 
skin 
hyperpigmentation 
X 
X 
X 
X 
X 
X 
Presence or absence of 
minocycline-induced 
skin staining 
X 
X 
X 
X 
X 
X 
Photography 
X 
X 
X 
X 
X 
X 
X 
Test Product 
Dispensed to Subject 
along with subject’s 
instructions 
X 
X 
X 
X 
X 
Subject Dairy 
Distribution/Collectio 
n/Review 
X 
X 
X 
X 
X 
X 
Collect All Study 
Medication Supplies / 
Drug Accountability 
X 
X 
X 
X 
X 
Collect and Record 
Adverse Events 
X 
X 
X 
X 
X 
X 
Subject Satisfaction 
Questionnaire 
X 
FSH = follicle-stimulating hormone; HIPAA = Health Insurance Portability and Accountability Act of 
1996. 
1Include height and weight. Height will be measured only at screening. 
2Include FSH levels (at screening only) for female subjects who have had a cessation of menses for at 
least 12 months but less than 24 months. 
3Female subjects of childbearing potential only (including pre-puberty). 
4Cutaneous Tolerance Score 
- Observer reported: erythema, scaling-peeling, edema. 
- Self-Reported: tightness, burning, stinging, itching. 
5Subjects should be instructed to call the office to schedule a visit as soon as acne recurrence is noted. 
Subjects should also be instructed to avoid any acne treatments until the final in office evaluation has 
been made. 


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8 
STUDY ASSESSMENTS 
8.1 
Efficacy Assessments 
Clinical evaluations of acne vulgaris will be performed by an experienced and qualified 
dermatologist (board certified or equivalent) or designee. To ensure consistency and reduce 
variability, the same assessor should perform all assessments on a given subject whenever 
possible. 
 
The following points must be noted regarding to the order of the efficacy assessments: 
 
• PROs (Patient Global Impression Questionnaires) should be completed prior to any other 
assessments to avoid bias in the subject’s evaluation. 
• The assessment of the IGA should be performed before the lesion counts. 
• Acne lesion counts are to be performed after the PROs and IGA evaluations. 
• Baseline assessments should be performed prior to first product administration. 
The time when each assessment is performed will be documented in the source document and/or 
eCRF. 
 
8.1.1 Acne Lesion Counts 
 
The number of acne lesions on the face (papules, pustules, nodules, and open and closed 
comedones) will be counted at every visit, according to the following definitions. The nose is 
excluded for the comedone counts. 
 
Inflammatory lesions: 
Papule: A small, solid elevation 5 mm or less in diameter. 
 
Pustule: A small, circumscribed elevation of the skin that contains yellow-white 
exudate. 
 
Nodule:  A circumscribed, elevated, lesion generally more than 5 mm in diameter. 
 
Noninflammatory lesions: 
Open comedone: 
A mass of sebaceous material that is impacted behind an open 
follicular orifice (blackhead) 
 
Closed comedone: A mass of sebaceous material that is impacted behind a closed 
follicular orifice (whitehead) 
 
Subjects will be examined in a well-lit room and without the aid of magnifying instruments. 
Total number of lesions and number of each type of lesion (papule, pustule, nodule, closed and 
open comedone) should be reported. 


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8.1.2 Investigator Global Assessment (IGA) 
 
The Investigator’s Global Assessment (IGA) of Disease Severity will be assessed at every study 
visit. The IGA is a global assessment of the current state of the disease. It is a 5-point 
morphological assessment of overall disease severity; assessment will be determined according 
to the following categories: 0 (clear), 1 (almost clear), 2 (mild severity), 3 (moderate severity) 
and 4 (severe). To be eligible, subjects must have an IGA score of 3 or 4 at the baseline (Day 0) 
visit. The IGA is an overall global evaluation of acne that should be performed at arm’s length 
distance from the patient. A detailed description of IGA scores is provided in Table 2. 
 
Table 2 : Investigator’s Global Assessment Scale for Acne Vulgaris 
 
Grade 
Description 
0 
Clear skin with no inflammatory or noninflammatory lesions 
1 
Almost clear; rare noninflammatory lesions with no more than one small inflammatory lesion 
2 
Mild severity; greater than Grade 1; some noninflammatory lesions with no more than a few 
inflammatory lesions (papules/pustules only, no nodular lesions) 
3 
Moderate severity; greater than Grade 2; up to many noninflammatory lesions and may have 
some inflammatory lesions, but no more than one small nodular lesion 
4 
Severe; greater than Grade 3; up to many noninflammatory and inflammatory lesions, but no 
more than a few nodular lesions 
Source: FDA Draft guidance on Acne Vulgaris 9 
 
8.1.3 Patient-Reported Outcomes (PROs) 
 
8.1.3.1 Patient Global Impression of Severity (PGI-S) 
 
The patient global impression of severity is a single-item question that asks the subject to rate the 
current severity of his or her acne. It will be assessed at baseline (Day 0), and at the Week 1, 2, 4, 
8, and 12 visits. 
 
Overall, how would you rate the severity of your acne now? 
 
The responses are as follows10: 
 
1. Clear skin 
2. Mild 
3. Moderate 
4. Severe 


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8.1.3.2 Patient Global Impression of Improvement (PGI-I) 
 
The patient global impression of improvement is a single-item question that asks the subject to 
rate the current symptom severity compared with how it was before taking the study medication 
(“Very much better” to “Very much worse”). It will be assessed at the Week 1, 2, 4, 8 and 12 
visits. 
 
Overall, how would you rate the change in severity of your acne compared with how it was 
before you started taking the medication in this study? 
 
The responses are as follows10: 
 
1. Very much better 
2. Much better 
3. A little better 
4. No change 
5. A little worse 
6. Much worse 
7. Very much worse 


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8.1.4 Photographic Documentation 
 
Photographic documentation of changes from baseline in the disease condition will be performed 
at baseline, weeks 1, 2, 4, 8, 12 and at the follow-up visit. Every effort will be made to 
standardize lighting, facial orientation, and distance from the camera to minimize between 
assessment variability due to image capture. 
 
8.2 
Safety Assessments 
 
8.2.1 Vital Signs 
 
The following vital signs will be recorded at screening and Week 12 visits (exit visit) in a seated 
position, after having sat calmly for at least 5 minutes: systolic and diastolic blood pressure 
(mmHg), pulse (bpm) and body temperature (°C). 
 
Weight (kg) and height (cm) will be recorded at the screening visit. The weight will also be 
recorded at the Week 12 visit (exit visit). 
 
Any abnormal finding related to vital signs that the investigator considers to be clinically 
significant, must be recorded as an AE. 
 
8.2.2 Brief Physical Examination 
 
The following sites/systems will be included in the brief physical examination that will be 
performed at screening and Week 12 visits (exit visit). Each system will be scored as 
normal/abnormal (non-clinically significant or clinically significant). Pertinent details must be 
recorded for any clinically significant findings. 
 
• General appearance 
• Dermatological (except acne on the face) 
• Respiratory 
• Cardiovascular 
• Abdominal 
 
8.2.3 Clinical Laboratory Tests 
 
Laboratory tests will be performed at screening and at Week 12. The tests will include 
hematology with differential and a standard chemistry panel (chemistry includes liver function 
tests). In addition, at the screening, baseline (Day 0), a urine pregnancy test will be performed for 
female subjects of childbearing potential (including pre-puberty) at the investigator site. The 
specific tests in these panels are listed in Table 3. 


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Table 3 Clinical Laboratory Testing 
 
Laboratory Testing 
Tests Included 
Hematology 
Basophils, Eosinophils, HCT, HGB, Lymphocytes, MCH, MCV, 
MCHC, Monocytes, Neutrophils, platelets, RBC, WBC 
Serum chemistry 
Albumin, Alkaline Phosphatase, ALT, AST, Chloride, CK, Creatinine 
(Enzymatic), GGT, Glucose Random, LDH, Potassium, Sodium, Total 
Bilirubin, Urea (BUN), Uric Acid 
Urine pregnancy test 
For females of childbearing potential (screening, baseline (Day 0) and 
Week 12 visits (exit visit)) 
Laboratory 
tests 
required at screening 
only 
FSH levels for female subjects who have had a cessation of menses for 
at least 12 months but less than 24 months. 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CK = 
creatine kinase; FSH = follicle-stimulating hormone; GGT = gamma-glutamyl transferase; HCT = 
hematocrit; HGB = hemoglobin; LDH = lactate dehydrogenase; MCH = mean corpuscular hemoglobin; 
MCV = mean corpuscular volume; RBC = red blood cell (count); WBC = white blood cell (count). 
 
Details about the collection and storage of clinical laboratory samples will be provided in the 
laboratory manual. 
 
8.2.4 Cutaneous Tolerance Scores 
 
Grading of local site reactions/tolerance will be performed at baseline (Day 0), and at Weeks 1, 
2, 4, 8, and 12 and at the follow-up visit. At the baseline (Day 0) visit, the tolerance assessments 
are to be performed before the drug application. 
 
The investigator (or qualified evaluator) will assess the presence and degree of erythema, 
scaling-peeling and edema at the application site using a 4-point scale, where 0=None, 1= Mild, 
2= Moderate, and 3=Severe. 
 
Erythema: 
0 – None 
No evidence of erythema present 
1 – Mild 
Slight pink coloration 
2 – Moderate 
Definite redness 
3 – Severe 
Marked erythema, bright red to dusky dark red in color 
 
Scaling-peeling: 
0 – None 
No scaling 
1 – Mild 
Barely perceptible, fine scales present to limited areas of the face 
2 – Moderate 
Fine scale generalized to all areas of the face 


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3 – Severe 
Scaling and peeling of skin over all areas of the face 
 
Edema: 
0 – None 
No edema 
1 – Mild 
Slight edema, barely perceptible 
2 – Moderate 
Definite edema, raised approximately 1mm. 
3 – Severe 
Severe edema, raised more than 1mm and beyond exposure area 
 
The subjects will be asked to grade their feeling of burning, stinging, tightness, and itching at the 
application site using a 4-point tolerability scale, where 0=None, 1= Mild, 2= Moderate, and 
3=Severe. 
 
Burning: 
0 – None 
No burning 
1 - Mild 
Slight burning sensation; not really bothersome 
2 – Moderate 
Definite warm, burning sensation that is somewhat bothersome 
3 – Severe 
Hot burning sensation that causes definite discomfort and may interrupt 
daily activities and/or sleep 
 
Stinging: 
0 – None 
No stinging 
1 – Mild 
Slight stinging sensation, not really bothersome 
2 – Moderate 
Definite stinging sensation that is somewhat bothersome 
3 – Severe 
Stinging sensation that causes definite discomfort and may interrupt daily 
activities and/or sleep 
 
Tightness: 
0 – None 
No tightness 
1 – Mild 
Slight tightness sensation, not really bothersome 
2 – Moderate 
Definite tightness sensation that is somewhat bothersome 
3 – Severe 
Tightness sensation that causes definite discomfort and may interrupt daily 
activities and/or sleep 
 
 
Itching: 
0 – None 
No itching 
1 – Mild 
Slight itching, not really bothersome 
2 – Moderate 
Definite itching that is somewhat bothersome 
3 – Severe 
Intense itching that may interrupt daily activities and/or sleep 


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8.2.5 Incidence 
of 
Minocycline-Induced 
Skin 
Hyperpigmentation, 
Visual 
Disturbances/Headaches Suggestive of Pseudotumor Cerebri 
Incidence of minocycline-induced skin hyperpigmentation, visual disturbances/headaches 
suggestive of pseudotumor cerebri will be evaluated by the investigator at Week 0, 1, 2, 4, 8 and 
12 visits as follows: 
 
1) Presence or absence of minocycline-induced skin hyperpigmentation. 
2) Presence or absence of headaches suggestive of pseudotumor cerebri. 
3) Presence or absence of visual disturbances suggestive of pseudotumor cerebri. 
 
Any occurrences of these specific events will be reported as an AE. 
 
If a subject reports headaches and/or visual disturbances suggestive of pseudotumor cerebri, the 
investigator should consider referral to a neurologist and must promptly contact the Medical 
Monitor to discuss the course of action. 
 
8.2.6 Incidence of Product Related Facial Staining 
 
This evaluation should occur prior to product administration at the baseline visit. Incidence of 
product-related skin staining will be evaluated by the investigator at Week 0, 1, 2, 4, 8 and 12 
visits and recorded as presence or absence of product-related skin staining. If staining is present, 
photographic documentation of the stained area will be obtained. Note that care should be taken 
to differentiate between actual staining (yellowish discoloration that does not wash off) vs. 
superficial 
accumulation 
of 
product 
(washes 
off) 
or 
hyperpigmentation 
(actual 
purplish/blue/black discoloration of tissues). 


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9 
ADVERSE EVENTS 
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical 
product, without regard to the possibility of a causal relationship with this treatment. 
 
Investigators are responsible for monitoring the safety of subjects who are participating in this 
study and for alerting the sponsor of any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the subject. The investigator is responsible for appropriate 
medical care of subjects during the study. 
 
The investigator remains responsible for following through an appropriate health care option for 
adverse events that are serious or that cause the subject to discontinue before completing the 
study. The subject should be followed until the event is resolved or stable. Follow-up frequency 
is left to the discretion of the investigator. 
 
Safety will be evaluated by collecting adverse events, recording vital signs, performing a brief 
physical examination, and evaluating laboratory results. The reported adverse events will be 
coded according to type and body system. 
 
Prior to enrollment, study site personnel will note the occurrence and nature of each subject’s 
medical condition(s) in the appropriate section of the source document and CRF. During the 
study, site personnel will again note any change in the condition(s) and the occurrence and nature 
of any adverse events. 
 
Any events occurring prior to the baseline visit will be recorded on the Medical History CRF. 
Events occurring after application of the 1st dose of study drug or those that increase in severity 
or frequency will be recorded as treatment-emergent adverse events (TEAEs) on the Adverse 
Event CRF. All AEs will be described in the source documents and in the CRF. 
 
9.1 
Adverse Events Causality 
The investigator will establish causality of the AE to experimental treatment. The investigator 
should take into account the subject’s history, most recent physical examination findings, and 
concomitant medications. 
 
The following definitions will be used to determine causality of an AE: 
 
- 
Not related: temporal relationship of the onset of the AE, relative to the experimental 
treatment is not reasonable or another cause can explain the occurrence of the AE. 
- 
 
Possibly related: temporal relationship of the onset of the AE, relative to the 
experimental treatment is possibly reasonable, follows a known response pattern to the 
treatment to suggest a causal relationship 


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- 
Related: temporal relationship of the onset of the AE, relative to the experimental 
treatment is reasonable, follows a known response pattern to the treatment, and an 
alternative cause is unlikely. 
 
9.2 
Adverse Events Severity 
The intensity of an AE is an estimate of the relative severity of the event made by the 
investigator based on his or her clinical experience and familiarity with the literature. The 
following definitions are to be used to rate the severity of an AE: 
 
- 
Mild: The symptom is barely noticeable to the subject and does not influence 
performance of daily activities. Treatment is not ordinarily indicated. 
 
- 
Moderate: The symptom is sufficiently severe to make the subject uncomfortable, and 
performance of daily activities is influenced. Treatment may be necessary. 
 
- 
Severe: The symptom causes severe discomfort, and daily activities are significantly 
impaired or prevented. Treatment may be necessary. 
 
9.3 
Serious Adverse Events 
If a subject experiences a serious adverse event after the first study product administration the 
event will be recorded as a serious adverse event in the source document and eCRF. 
 
A serious adverse event (experience) or reaction is any untoward medical occurrence that at any 
dose: 
 
• 
results in death, 
 
• 
is life-threatening, 
 
• 
requires in-patient hospitalization or prolongation of existing hospitalization, 
 
• 
results in persistent or significant disability/incapacity, or 
 
• 
is a congenital anomaly/birth defect. 
 
NOTE: The term “life-threatening” in the definition of “serious” refers to an event in which 
the subject was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may require 


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intervention to prevent one of the other outcomes listed in the definition above. These should 
also usually be considered serious. 
 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse. 
 
9.3.1 SAE Reporting 
 
BioPharmX will be in charge of the overall pharmacovigilance process for the present study. All 
SAEs, related or not, occurring during the course of the study must be reported to BioPharmX on 
an SAE form within 24 hours of the knowledge of the occurrence (this refers to any AE that 
meets one or more of the aforementioned serious criteria). 
 
Reporting should be done by sending the completed SAE Report Form to the following email 
address: 
Safety Contact Information: AnnaMarie Daniels (Medical Monitor) 
E-mail: amdaniels@biopharmx.com 
Telephone: 310-701-2080 
The Medical Monitor will evaluate all SAEs as soon as the reports are received and will assess 
the expectedness of each SAE to the study treatment. For each SAE received, the Medical 
Monitor will make a determination as to whether the criteria for expedited reporting to relevant 
regulatory authorities have been met. The sponsor will manage the expedited reporting of 
relevant safety information to concerned regulatory agencies in accordance with local laws and 
regulations. 
 
9.4 
Pregnancy Reporting 
If a female subject becomes pregnant during the study, the subject should inform the study site as 
soon as possible. Upon confirmation of the pregnancy, the female subject will be discontinued 
from the study. The investigator must complete a study-specific Pregnancy Form upon 
confirmation of a pregnancy and send it to BioPharmX within 24 hours of confirmation of the 
pregnancy (contact information to be used is the same as for SAE reporting). Post-treatment 
follow-up should be done to ensure subject safety. Pregnancy is not itself an AE or SAE; 
however, maternal/fetal complications or abnormalities will be recorded as AEs or SAEs, as 
appropriate. The investigator will follow the pregnancy until completion or until pregnancy 
termination and, in the case of a liveborn offspring, to 1 month of age of that infant and notify 
BioPharmX of the outcome as a follow-up to the initial Pregnancy Form. All pregnancies should 
be reported to the sponsor and ethics committee. 


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10 
SAMPLE SIZE AND STATISTICAL METHODS 
10.1 Determination of Sample Size 
This small sample size is expected to provide only directional information and no statistical 
significance is expected for any outcome measure. 
 
10.2 Statistical and Analytical Plans 
Descriptive summaries of demographics, baseline characteristics and subject disposition will be 
presented. Outcomes data for each subject and each treatment group will be presented in tabular 
form. 
 
10.2.1 Analysis Populations 
 
Efficacy will be evaluated on the basis of the intent-to-treat (ITT) population. A supportive 
analysis will also be conducted on the per-protocol (PP) population. 
 
All subjects who received at least one dose of the medication will be included in the ITT 
population. All subjects will be analyzed according to the treatment group to which they were 
assigned. 
 
The per-protocol (PP) population will include all subjects who were treated with no significant 
protocol deviations and who provided evaluable data for the primary endpoint (absolute change 
from baseline in inflammatory lesions count at Week 12). 
 
The safety population (SAF) will be defined as all subjects who received at least one dose of the 
medication. Analysis will be performed according to the actual treatment they received. 
 
10.2.2 Subject Disposition 
 
Descriptive summaries of demographic, baseline characteristics and subject disposition will be 
presented. The protocol deviations will be summarized by treatment and category. 
 
10.2.3 Efficacy Analysis 
 
10.2.3.1 
Primary Analysis 
 
Absolute change from baseline at Week 12 in inflammatory lesion count for each subject will be 
presented in tabular form. The mean change for each group will be compared but any 
conclusions are expected to be directional in nature only and not statistically significant. 


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10.2.3.2 
Secondary and Exploratory Analyses 
 
The secondary and exploratory efficacy endpoints will be presented in tabular form and 
examined for trends. 
 
10.2.3.3 
Safety Analysis 
 
All safety data, including AEs and SAEs will be presented and tabulated according to type and 
body system classification. Descriptions of AEs will include the date of onset, the date the AE 
ended (if it resolved), the severity and seriousness of the AE, the causality of the AE to study 
drug, and the outcome. The focus in this protocol will be the incidence of treatment emergent 
adverse events (TEAEs). 
 
Reported AEs will be summarized by the number of subjects reporting the events, as well as by 
System Class, severity, seriousness, and relationship to study medication. For the summary of 
AEs by severity, each subject will be counted only once within a System Class or type by using 
the AEs with the highest intensity within each category for each analysis. For the summary of 
AEs by relationship to study medication, each subject will be counted only once within a System 
Class or a type by using the AEs with the greatest reported relationship within each category. For 
the summary of AEs by relationship to study medication and severity, each subject will be 
counted only once within a System Class or a type by using (1) the greatest reported relationship 
followed by (2) the highest reported intensity. 
 
All information pertaining to AEs noted during the study will be listed by subject, detailing 
verbatim, System Class, type, start date, stop date, intensity, outcome and relationship to study 
drug. The AE onset will also be shown relative (in number of days) to the day of test article 
administration. Serious adverse events (SAEs) will be tabulated by treatment group, relationship 
to the test article, and a reference to the occurrence of the SAEs to the relative day of dosing. 
 
Incidence of minocycline-induced skin hyperpigmentation, visual disturbances/headaches 
suggestive of pseudotumor cerebri, and product related staining will be summarized and 
presented descriptively by treatment group. 
 
Concomitant medications will be listed by subject. 
 
In addition, a list of subjects who discontinued from the study will be provided. 
 
Shift tables describing shifts to clinically significant out of normal range will be provided for 
clinical laboratory results and normal-abnormal shift tables will be provided for vital signs. 
 
Local cutaneous tolerability scores will be tabulated by treatment and visit using descriptive 
statistics. 


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10.2.4 Interim Analysis 
 
No formal interim analysis is planned for this study. 


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11 
DATA QUALITY ASSURANCE/SITE MONITORNG 
During the study, BioPharmX or representatives will conduct monitoring visits at regular 
intervals. The monitoring visits will be conducted to ensure protocol adherence, quality of data, 
accuracy of entries on the CRFs, drug accountability, compliance with regulatory requirements 
and continued adequacy of the investigational site and its facilities. 
 
The site may be audited and/or monitored by a quality assurance officer named by the sponsor 
and/or regulatory authorities may wish to perform on-site audits. The investigator will be given 
notice before an audit occurs and will be expected to cooperate with any audit, and provide 
assistance and documentation (including source data) as requested. 
 
12 
DATA COLLECTION AND RETENTION 
Subject data will be entered by site personnel using paper CRFs. 
 
The investigator must maintain source documents for each subject in the study to support any 
information or evaluations that are not performed solely for the study and are not recorded 
directly into the study CRFs. 
 
13 
CONFIDENTIALITY OF TRIAL DOCUMENTS AND 
SUBJECT RECORDS 
The investigator must assure that the subjects’ anonymity will be maintained and that their 
identities are protected from unauthorized parties. On CRFs or other documents, including 
photographs, submitted to the sponsor, subjects should not be identified by their names, but by 
an identification code. The investigator should keep a subject enrolment log relating codes with 
the names of subjects. The investigator should maintain documents not for submission to 
BioPharmX (e.g., subjects’ written consent forms) in strict confidence. 
 
14 
INVESTIGATOR’S FILES AND RETENTION OF 
DOCUMENTS 
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into two different separate categories: investigator study file and subject clinical 
source documents. 
 
The records should be retained by the investigator according to International Conference on 
Harmonisation (ICH), local regulations, or as specified in the Clinical Trial Agreement (CTA), 
whichever is longer. 
 
15 
ETHICS 


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15.1 Local Regulations/Declaration of Helsinki 
This study will be conducted in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki (2008) and that are consistent with “Good Clinical Practice” ICH 
Tripartite Guideline (July 2002) and the applicable laws and regulations of the country in which 
the research is conducted, whichever affords the greater protection to the individual. 
 
15.2 Ethical Review 
It is the understanding of the sponsor that this protocol (and any amendments) as well as 
appropriate consent procedures, will be reviewed and approved by a research ethics board/ 
institutional review board (REB/IRB). This board must operate in accordance with the current 
federal regulations. For sites with local ethics committee, a letter or certification of approval will 
be sent by the investigator to the sponsor prior to initiation of the study, and also whenever 
subsequent modifications to the protocol are made. 
 
15.3 Informed Consent 
It is the responsibility of the investigator, or a person designated by the investigator (if 
acceptable by local regulation), to obtain written informed consent from each individual 
participating in this study, after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study. It must also be explained to the subjects that they are completely 
free to refuse to enter the study or to withdraw from it at any time for any reason. 
 
If new safety information results in significant changes in the risk/benefit assessment or any new 
information that may affect willingness to continue to participate, the consent form should if 
necessary be reviewed and updated by the (REB/IRB). All subjects (including those already 
being treated) should be informed of the new information, given a copy of the revised form and 
asked to give their consent to continue in the study. 
 
16 
PUBLICATION POLICY 
The publication policy will be addressed in the Research and Financial agreement, and all details 
outlined in the agreement will apply to this protocol. 


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17 
REFERENCES 
 
1. 
Leyden JJ. A review of the use of combination therapies for the treatment of acne 
vulgaris. J Am Acad Dermatol. 2003;49(3 Suppl):S200-10. 
2. 
Bhate K, Williams HC. Epidemiology of acne vulgaris. The British journal of 
dermatology. 2013;168:474-85. 
3. 
Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. Management of 
acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad 
Dermatol. 2003;49(1 Suppl):S1-37. 
4. 
Weiss JS. Acne: evolving concepts of pathogenesis need to guide therapeutic 
developments. J Drugs Dermatol. 2013; 12: s66. 
5. 
Minocycline Topical Gel BPX-01, Investigator Brochure, BioPharmX, January 25, 2016. 
6. 
Medicis, Product Information of Solodyn (minocycline hydrochloride) (2013). 
7. 
I. Chopra, M. Roberts, Tetracycline Antibiotics: Mode of Action, Applications, 
Molecular Biology, and Epidemiology of Bacterial Resistance. Microbiol. Mol. Biol. 
Rev. 2001; 65:232–260. 
8. 
M. Jonas, B. Cunha, Minocycline. Therapeutic Drug Monitoring. 1982; 4:137–145. 
9. 
Food and Drug Administration : Draft guidance on Acne Vulgaris: Developing Drugs for 
Treatment (September 2005), Available from: 
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidanc 
es/ucm071292.pdf 
10. 
Yalcin I, Bump R. Validation of two global impression questionnaires for incontinence. 
Am J Obstet Gynecol. 2003;189:98-101.