Neurogenic Detrusor Overactivity
Conditions
Keywords
Phase I, Fesoterodine beads- in-capsule, bioequivalence, Pharmacokinetics, Toviaz
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.
Interventions
DRUG4 mg Fesoterodine ER tablet from Zwickau
Manufactured at Zwickau
DRUG4 mg fesoterodine ER tablet from Freiburg
Manufactured at Freiburg
DRUG8 mg fesoterodine ER tablet from Zwickau
Manufactured at Zwickau
DRUG8 mg fesoterodine ER tablet from Freiburg
Manufactured at Freiburg
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | Maximum Observed Plasma Concentration (Cmax) of 5-Hydroxymethyl-tolterodine (5-HMT) |
| AUCinf (if data permit, otherwise AUClast) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | Area Under the Curve From Time Zero to Extrapolated Infinite Time \[AUC (0 - ∞)\] of 5-Hydroxymethyl-tolterodine (5-HMT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | Plasma Decay Half-Life (t1/2) of 5-Hydroxymethyl-tolterodine (5-HMT) |
| 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 | — |
| AUCLast | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of 5-Hydroxymethyl-tolterodine (5-HMT) |
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities | During screening | — |
| 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 | — |
| Tmax | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours | Time to Reach Maximum Observed Plasma Concentration (Tmax) of 5-Hydroxymethyl-tolterodine (5-HMT) |
Countries
Belgium
Outcome results
None listed