An Open-label Trial to Evaluate Mass Balance of Tavapadon at Steady State in Healthy Subjects

NCT04241393 | Completed Phase 1 FDA Drug

• 1 other identifier: CVL-751-HV-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to determine the absorption, metabolism, and excretion (AME) of \[14C\] tavapadon.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (20)

• Pharmacokinetics of [14C]-Tavapadon and Metabolites: Area under the radioactivity time curve from zero to infinity (AUCinf) for Tavapadon and Metabolites (PF-06752844), in plasma and whole blood

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon and Metabolites: Area under the radioactivity time curve from time 0 to last quantifiable concentration (AUClast) for Tavapadon and Metabolites (PF-06752844), in plasma and whole blood

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon and Metabolites: Peak radioactivity Cmax) for Tavapadon and Metabolites (PF-06752844), in plasma and whole blood

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon and Metabolites: Time to last measurable radioactivity (Tlast) for Tavapadon and Metabolites (PF-06752844), in plasma and whole blood

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon and Metabolites: Time to maximum radioactivity (Tmax) for Tavapadon and Metabolites (PF-06752844), in plasma and whole blood

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon and Metabolites: elimination half-life (t½) for Tavapadon and Metabolites (PF-06752844), in plasma and whole blood

  Day 16 up to Day 28

• Pharmacokinetics of Tavapadon: Apparent total body clearance (CL/F) for Tavapadon

  Day 16 up to Day 28

• Pharmacokinetics of Tavapadon: Apparent volume of distribution (Vz/F) for Tavapadon

  Day 16 up to Day 28

• Ratio of Plasma AUCinf for Tavapadon to whole blood total Radioactivity AUCinf

  Day 16 up to Day 28

• Ratio of Plasma AUCinf for Metabolites (PF-06752844) to whole blood total Radioactivity AUCinf

  Day 16 up to Day 28

• Ratio of plasma AUCinf for Metabolites (PF-06752844) to plasma AUCinf for Tavapadon

  Day 16 up to Day 28

• Ratio of whole blood AUCinf for Tavapadon (and metabolites, measured as total radioactivity) to plasma AUCinf for Tavapadon (and metabolites, measured as total radioactivity)

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon: Total radioactivity in urine at different intervals

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon: Cumulative radioactivity excreted in urine (Cumulative Aeu)

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon: Fraction of the dose administered excreted in urine (Feu) for total radioactivity at different intervals

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon: Cumulative fraction of the dose administered excreted in urine (Cumulative Feu) for total radioactivity in urine

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon: Amount eliminated in feces (Aef) for total radioactivity in feces at different intervals

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon: Cumulative amount excreted in feces (Cumulative Aef) for total radioactivity in feces

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon: Fraction of the dose administered excreted in feces (Fef) for total radioactivity in feces at different intervals

  Day 16 up to Day 28

• Pharmacokinetics of [14C]-Tavapadon: Cumulative Fraction of the dose administered excreted in feces (Cumulative Fef) for total radioactivity in feces

  Day 16 up to Day 28

Secondary Outcomes (5)

• Number of Subjects with reported Treatment Emergent Adverse Events (TEAEs)

  Up to Day 28

• Number of subjects with Clinically significant changes in Electrocardiogram measures (PR,RR,QT and QTcF)

  Up to Day 28

• Number of subjects with Clinically meaningful changes in Vital signs (Systolic and Diastolic blood pressures, heart rate, respiratory rate and body temperature)

  Up to Day 28

• Number of subjects with clinically significant changes in laboratory measures

  Up to Day 28

• Change from baseline of the Columbia-Suicide Severity Rating Scale (C-SSRS)

  At Baseline and up to Day 28

Study Arms (1)

Tavapadon

EXPERIMENTAL

Drug: Tavapadon tablet; Drug: Tavapadon [14C] suspension

Interventions

Tavapadon tablet DRUG

Participants will receive multiple dose titration of Tavapadon (0.25 mg once daily \[QD\] on Days 1 to 3, 0.5 mg QD on Days 4 to 6, 1.0 mg QD on Days 7 to 9, 1.5 mg QD on Days 10 to 12, and 2.5 mg QD on Days 13 to 15)

Tavapadon

Tavapadon [14C] suspension DRUG

Following 15-Day multiple dose titration of Tavapadon, participants will receive a single oral dose of Tavapadon 2.5 mg containing approximately 100 μCi of \[14C\] Tavapadon on Day 16

Tavapadon

Eligibility Criteria

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

You may qualify if:

• Male subjects, ages 18 to 55 years, inclusive, at the time of signing the informed consent form (ICF).
• Body mass index (BMI) of 18.0 to 32.0 kg/m2 and a total body weight \> 50 kg (110 lbs).
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, Gilbert's syndrome\] is not acceptable) at Screening or Check-in as assessed by the investigator (or designee).
• Male subjects with a pregnant or a nonpregnant partner of childbearing potential must agree to use an acceptable or a highly effective method of contraception from signing of informed consent during the trial, and for 7 days following the last dose of study drug.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
• Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures.
• Capable of consuming the standard diet.
• History of a minimum of 1 bowel movement per day.

You may not qualify if:

• \- Medical History and Concurrent Diseases
• Has a history of psychotic symptoms requiring treatment with an antipsychotic medication within the 12 months prior to signing ICF.
• Subjects with epilepsy, or history of epilepsy, or conditions that lower seizure threshold, seizures of any etiology (including substance or drug withdrawal), or who have increased risk of seizures as evidenced by history of electroencephalogram with epileptiform activity. Subjects with a history of febrile seizures and/or history of head trauma with loss of consciousness requiring hospitalization overnight will be excluded as well.
• Subjects with a current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological disease that, in the opinion of the investigator or medical monitor, could compromise either subject safety or the results of the trial.
• Medical conditions that are minor or well controlled may be considered acceptable if the condition does not expose the subject to an undue risk of a significant AE or interfere with the assessments of safety during the course of the trial. The medical monitor should be contacted in any instance where the investigator is uncertain regarding the stability of a subject's medical conditions(s) and the potential impact of the condition(s) on trial participation.
• Any condition possibly affecting drug absorption including history of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed; cholecystectomy and bariatric weight loss surgeries will not be allowed).
• History of substance or alcohol-use disorder (excluding nicotine; Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria) within 2 years prior to signing the ICF.
• History of regular alcohol consumption exceeding 14 drinks/week \[1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor\] within 6 months prior to signing ICF.
• Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.
• Subjects who answer "yes" on the Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting the criteria for C-SSRS Item 4 or Item 5 occurred within the last 6 months, OR
• Subjects who answer "yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting the criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR
• Subjects who, in the opinion of the investigator, present a serious risk of suicide.
• Subjects who have attempted suicide in the past.
• \- Physical Examination and Clinical Laboratory Results
• Positive hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody) and/or positive human immunodeficiency virus test (HIV-1 and HIV-2 antibody) at Screening.

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead

Study Sites (1)

Covance Clinical Research Unit, Inc.

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

Suspensions

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Matthew Leoni, MD

  Cerevel Therapeutics, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: January 27, 2020
• Study Start: February 4, 2020
• Primary Completion: November 8, 2020
• Study Completion: November 8, 2020
• Last Updated: November 17, 2020

Record last verified: 2020-11

Locations

US (1)