Clinical trial NCT04478357: BIOEQUIVALENCE STUDY IN HEALTHY PARTICIPANTS COMPARING 4 MG AND 8 MG FESOTERODINE EXTENDED-RELEASE TABLETS (TOVIAZ™), MANUFACTURED AT ZWICKAU VERSUS FREIBURG
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neurogenic Detrusor Overactivity
Keywords: Phase I
Fesoterodine beads- in-capsule
bioequivalence
Pharmacokinetics
Toviaz
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-07-20
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Cmax
timeFrame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
measure: AUCinf (if data permit, otherwise AUClast)
timeFrame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
Secondary outcomes:
measure: AUCLast
timeFrame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
measure: Tmax
timeFrame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
measure: t1/2
timeFrame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
timeFrame: 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
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: 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
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities
timeFrame: During screening
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Brussels Clinical Research Unit
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: