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

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

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.

Study Overview

• Status: Completed
• Conditions: Neurogenic Detrusor Overactivity
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Brussels Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female participants must be 18 to 55 years of age, inclusive, at the time of signing the informed consent document (ICD).
2. 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.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
4. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
5. 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

1. 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).
2. Any condition possibly affecting drug absorption (eg, gastrectomy).
3. 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.
4. 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.
5. History of allergy or hypersensitivity to fesoterodine fumarate or tolterodine tartrate, soya, or any of the excipients in the investigational drug product.
6. History of uncontrolled narrow angle glaucoma, myasthenia gravis, gastric retention, severe ulcerative colitis and toxic megacolon.
7. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment A; 4 mg fesoterodine ER tablet manufactured at Zwickau.	Drug: 4 mg Fesoterodine ER tablet from Zwickau; Manufactured at Zwickau
Other: Treatment B; 4 mg fesoterodine ER tablet manufactured at Freiburg	Drug: 4 mg fesoterodine ER tablet from Freiburg; Manufactured at Freiburg
Other: Treatment C; 8 mg fesoterodine ER tablet manufactured at Zwickau	Drug: 8 mg fesoterodine ER tablet from Zwickau; Manufactured at Zwickau
Other: Treatment D; 8 mg fesoterodine ER tablet manufactured at Freiburg.	Drug: 8 mg fesoterodine ER tablet from Freiburg; Manufactured at Freiburg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Actual): November 12, 2020
• Study Completion (Actual): November 12, 2020

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): May 7, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase I; bioequivalence; Toviaz; Fesoterodine beads- in-capsule
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Fesoterodine
• Other Study ID Numbers: A0221106; 2014-002783-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No