BIOEQUIVALENCE STUDY IN HEALTHY PARTICIPANTS COMPARING 4 MG AND 8 MG FESOTERODINE EXTENDED-RELEASE TABLETS (TOVIAZ™), MANUFACTURED AT ZWICKAU VERSUS FREIBURG

Study Overview
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Brief Summary
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Fesoterodine (Toviaz™) extended-release (ER) tablets are currently manufactured by Aesica Pharmaceuticals, Zwickau, Germany (Zwickau). An additional manufacturing location at Pfizer Freiburg, Germany (Freiburg) has been identified. This pivotal bioequivalence (BE) study is being conducted to satisfy the United States (US) Food and Drug Administration (FDA) regulatory requirements for the qualification of the Freiburg manufacturing site. Overall Study Design This is an open-label, randomized, single-dose, 4-period, 4-treatment, 2-sequence, two 2-way crossover study in healthy participants. This study will assess the BE of Fesoterodine (Toviaz™) 4 mg and 8 mg ER tablets manufactured at Zwickau (Reference) versus Freiburg (Test). Study participants will include healthy male and/or female individuals between the ages of 18 and 55 years, inclusive. Approximately 18 participants who fulfill entry criteria will be randomized to 1 of the 2 treatment sequences as shown in the table below.

Official Title
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AN OPEN-LABEL, RANDOMIZED, SINGLE-DOSE, 4 PERIOD, 4 TREATMENT, 2 SEQUENCE, TWO 2 WAY CROSSOVER, BIOEQUIVALENCE STUDY IN HEALTHY PARTICIPANTS COMPARING 4 MG AND 8 MG FESOTERODINE EXTENDED RELEASE TABLETS (TOVIAZ(TM)), MANUFACTURED AT ZWICKAU VERSUS FREIBURG

Conditions
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Neurogenic Detrusor Overactivity

Intervention / Treatment
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* Drug: 4 mg Fesoterodine ER tablet from Zwickau
* Drug: 4 mg fesoterodine ER tablet from Freiburg
* Drug: 8 mg fesoterodine ER tablet from Zwickau
* Drug: 8 mg fesoterodine ER tablet from Freiburg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants must be 18 to 55 years of age, inclusive, at the time of signing the informed consent document (ICD). Male and female participants who are overtly healthy as determined by medical evaluation including a detailed medical history, complete physical examination, cardiovascular tests including blood pressure (BP), pulse rate measurement and 12-lead ECG, and clinical laboratory tests. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol. Exclusion Criteria Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Any condition possibly affecting drug absorption (eg, gastrectomy). History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C infection; positive testing for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. History of allergy or hypersensitivity to fesoterodine fumarate or tolterodine tartrate, soya, or any of the excipients in the investigational drug product. History of uncontrolled narrow angle glaucoma, myasthenia gravis, gastric retention, severe ulcerative colitis and toxic megacolon. Evidence or history of clinically significant urologic disease, urinary retention, obstructive disturbance of bladder emptying, micturition disturbance, nocturia or pollacisuria (eg, benign prostate hyperplasia, urethral stricture, recurrent urinary tract infections).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is an open-label, randomized, single-dose, 4-period, 4-treatment, 2-sequence, two 2-way crossover study in healthy participants. This study will assess the BE of Fesoterodine (Toviaz™) 4 mg and 8 mg ER tablets manufactured at Zwickau (Reference) versus Freiburg (Test). Study participants will include healthy male and/or female individuals between the ages of 18 and 55 years, inclusive. Approximately 18 participants who fulfill entry criteria will be randomized to 1 of the 2 treatment sequences as shown in the table below.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment A<br>4 mg fesoterodine ER tablet manufactured at Zwickau. | Drug: 4 mg Fesoterodine ER tablet from Zwickau<br>* Manufactured at Zwickau<br>|
| Other: Treatment B<br>4 mg fesoterodine ER tablet manufactured at Freiburg | Drug: 4 mg fesoterodine ER tablet from Freiburg<br>* Manufactured at Freiburg<br>|
| Other: Treatment C<br>8 mg fesoterodine ER tablet manufactured at Zwickau | Drug: 8 mg fesoterodine ER tablet from Zwickau<br>* Manufactured at Zwickau<br>|
| Other: Treatment D<br>8 mg fesoterodine ER tablet manufactured at Freiburg. | Drug: 8 mg fesoterodine ER tablet from Freiburg<br>* Manufactured at Freiburg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum Observed Plasma Concentration (Cmax) of 5-Hydroxymethyl-tolterodine (5-HMT) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | 
| AUCinf (if data permit, otherwise AUClast) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of 5-Hydroxymethyl-tolterodine (5-HMT) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCLast | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of 5-Hydroxymethyl-tolterodine (5-HMT) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | 
| Tmax | Time to Reach Maximum Observed Plasma Concentration (Tmax) of 5-Hydroxymethyl-tolterodine (5-HMT) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | 
| t1/2 | Plasma Decay Half-Life (t1/2) of 5-Hydroxymethyl-tolterodine (5-HMT) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | 
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) |  | Day -28 to day -1, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours, Day 28 to 35 and on early termination | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs |  | Day -28 to day -1, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours, Day 28 to 35 and on early termination | 
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities |  | During screening | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Fesoterodine beads- in-capsule, bioequivalence, Pharmacokinetics, Toviaz