Study To Assess The Bioequivalence Under Fed And Fasted Conditions Of The Fesoterodine Beads-In-Capsule SR4 And SR7 Formulations And To Estimate The Bioavailability of SR7 Beads Sprinkled On Apple Sauce Relative To The Beads-In-Capsule SR7 Formulation Administer

NCT04452838 | Completed Phase 1

• 2 other identifiers: A02211152019-001909-24
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Open Label, Single-Dose, Crossover Study To Assess The Bioequivalence Under Fed And Fasted Conditions Of The Fesoterodine Beads-In-Capsule (BIC) SR4 And SR7 Formulations And To Estimate The Bioavailability of SR7 Beads Sprinkled On Apple Sauce Relative To The Beads-In-Capsule SR7 Formulation Administered Intact.

Conditions

Neurogenic Detrusor Overactivity

Keywords

Phase I, Fesoterodine beads- in-capsule, Bioequivalence, Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• AUCinf of 5-HMT

  Area under the plasma concentration-time curve from time zero extrapolated to infinity.

  0 (pre dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 30, 36, and 48 hours

• AUClast of 5-HMT

  Area under the plasma concentration-time curve from 0 to the time of the last quantifiable concentration.

  0 (pre dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 30, 36, and 48 hours

• Cmax of 5-HMT

  Maximum Observed Plasma Concentration

  0 (pre dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 30, 36, and 48 hours

Study Arms (6)

Cohort 1 Sequence 1 (Part A)

OTHER

Treatment Sequence A,B,C and D

Drug: Fesoterodine BIC SR4 fasted (Treatment A in Part A, Treatment G in Part B); Drug: Fesoterodine BIC SR7 fasted (Treatment B in Part A, Treatment H in Part B); Drug: Fesoterodine BIC SR7 fed (Treatment C in Part A, Treatment F in Part B); Drug: Fesoterodine BIC SR7 on apple sauce (Treatment D in Part A)

Cohort 1 Sequence 2 (Part A)

OTHER

Treatment Sequence B, A,C and D

Drug: Fesoterodine BIC SR4 fasted (Treatment A in Part A, Treatment G in Part B); Drug: Fesoterodine BIC SR7 fasted (Treatment B in Part A, Treatment H in Part B); Drug: Fesoterodine BIC SR7 fed (Treatment C in Part A, Treatment F in Part B); Drug: Fesoterodine BIC SR7 on apple sauce (Treatment D in Part A)

Cohort 2 Sequence 1 (Part B)

OTHER

Treatment Sequence E, F, G, and H

Drug: Fesoterodine BIC SR4 fasted (Treatment A in Part A, Treatment G in Part B); Drug: Fesoterodine BIC SR7 fasted (Treatment B in Part A, Treatment H in Part B); Drug: Fesoterodine BIC SR7 fed (Treatment C in Part A, Treatment F in Part B); Drug: Fesoterodine BIC SR4 fed (Treatment E in Part B)

Cohort 2 Sequence 2 (Part B)

OTHER

Treatment Sequence E, F, H and G

Drug: Fesoterodine BIC SR4 fasted (Treatment A in Part A, Treatment G in Part B); Drug: Fesoterodine BIC SR7 fasted (Treatment B in Part A, Treatment H in Part B); Drug: Fesoterodine BIC SR7 fed (Treatment C in Part A, Treatment F in Part B); Drug: Fesoterodine BIC SR4 fed (Treatment E in Part B)

Cohort 2 Sequence 3 (Part B)

OTHER

Treatment Sequence F, E, G, and H

Drug: Fesoterodine BIC SR4 fasted (Treatment A in Part A, Treatment G in Part B); Drug: Fesoterodine BIC SR7 fasted (Treatment B in Part A, Treatment H in Part B); Drug: Fesoterodine BIC SR7 fed (Treatment C in Part A, Treatment F in Part B); Drug: Fesoterodine BIC SR4 fed (Treatment E in Part B)

Cohort 2 Sequence 4 (Part B)

OTHER

Treatment sequence F, E, H, and G

Drug: Fesoterodine BIC SR4 fasted (Treatment A in Part A, Treatment G in Part B); Drug: Fesoterodine BIC SR7 fasted (Treatment B in Part A, Treatment H in Part B); Drug: Fesoterodine BIC SR7 fed (Treatment C in Part A, Treatment F in Part B); Drug: Fesoterodine BIC SR4 fed (Treatment E in Part B)

Interventions

Fesoterodine BIC SR4 fasted (Treatment A in Part A, Treatment G in Part B) DRUG

4 mg administered under fasted condition.

Cohort 1 Sequence 1 (Part A); Cohort 1 Sequence 2 (Part A); Cohort 2 Sequence 1 (Part B); Cohort 2 Sequence 2 (Part B); Cohort 2 Sequence 3 (Part B); Cohort 2 Sequence 4 (Part B)

Fesoterodine BIC SR7 fasted (Treatment B in Part A, Treatment H in Part B) DRUG

4 mg administered under fasted conditions.

Cohort 1 Sequence 1 (Part A); Cohort 1 Sequence 2 (Part A); Cohort 2 Sequence 1 (Part B); Cohort 2 Sequence 2 (Part B); Cohort 2 Sequence 3 (Part B); Cohort 2 Sequence 4 (Part B)

Fesoterodine BIC SR7 fed (Treatment C in Part A, Treatment F in Part B) DRUG

4 mg administered under fed conditions.

Cohort 1 Sequence 1 (Part A); Cohort 1 Sequence 2 (Part A); Cohort 2 Sequence 1 (Part B); Cohort 2 Sequence 2 (Part B); Cohort 2 Sequence 3 (Part B); Cohort 2 Sequence 4 (Part B)

Fesoterodine BIC SR7 on apple sauce (Treatment D in Part A) DRUG

4 mg sprinkled on apple sauce administered under fasting conditions

Cohort 1 Sequence 1 (Part A); Cohort 1 Sequence 2 (Part A)

Fesoterodine BIC SR4 fed (Treatment E in Part B) DRUG

4 mg administered under fed conditions

Cohort 2 Sequence 1 (Part B); Cohort 2 Sequence 2 (Part B); Cohort 2 Sequence 3 (Part B); Cohort 2 Sequence 4 (Part B)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 medical history, physical examination, and laboratory tests.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Weight:
• 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

You may not qualify if:

• 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, cholecystectomy).
• History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody (HCVAb). A positive serology for hepatitis B surface antibody (HBsAb) as a result of 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 pollakiuria (eg, benign prostate hyperplasia, urethral stricture, recurrent urinary tract infections).
• Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product.
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer).
• A positive urine drug test, as confirmed by a single repeat.
• Screening supine blood pressure (BP) greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
• Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline corrected QT (QTc) interval \>450 msec, complete left bundle branch block \[LBBB\], signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree atrioventricular \[AV\] block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is greater than 450 msec, this interval should be rate-corrected using the Fridericia method and the resulting corrected QT (QTcF) should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants.
• Participants with ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:
• Screening estimated glomerular filtration rate (eGFR) is less than or equal to 90 mL /min/1.73 m2 for Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula).
• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Brussels Clinical Research Unit

Brussels, Bruxelles-capitale, Région de, B-1070, Belgium

Location

Related Links

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

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 1 randomized, open-label, single-dose crossover study in healthy participants. A two stage approach outlined below will be followed: Part A (Cohort 1): This part of the study is a 2 sequence, 4 period, crossover design. Part B (Cohort 2): This part of the study is a 4 sequence, 4 period, crossover design. Participants will be randomized to 1 of 4 possible treatment sequences. If bioequivalence (BE) criteria for the comparison of the BIC SR7 formulation with the BIC SR4 formulation administered in the fasted state are met in Part A, the formulations will be considered bioequivalent in the fasted state and only the first two periods of Part B will be conducted. Part B (all periods) may not be conducted if the AUCinf or Cmax Percent Geometric Mean Ratio GMR is less than 90% and greater than 111% and/or if variability suggest a highly variable drug (e.g., greater than 30%) because BE demonstration may not be possible with a reasonably sized 4 sequence 4 period study.

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: July 1, 2020
• Study Start: June 26, 2020
• Primary Completion: January 4, 2021
• Study Completion: January 4, 2021
• Last Updated: February 10, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)