A Study Investigating the Excretion Balance, Pharmacokinetics and Metabolism of a Single Oral Dose of [14C]-Labeled Risdiplam (RO7034067) in Healthy Male Participants

NCT03036501 | Completed Phase 1

• 2 other identifiers: BP391222016-003461-26
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, non-randomized study investigating the excretion balance, PK and metabolism of a single oral dose of \[14C\]-labeled Risdiplam (RO7034067) in healthy male participants. This study will assess the characterize mass balance, routes and rates of elimination of \[14C\]-labeled Risdiplam (RO7034067), using conventional analytical methods and assess the pharmacokinetics of total drug related \[14C\]-radioactivity, Risdiplam (RO7034067) and its metabolite(s).

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• Percentage of Dose Recovered as Total [14C]-radioactivity in Urine

  Day 1 to Day 36

• Cumulative Urinary Amount of Total [14C]-Radioactivity in Urine

  Day 1 to Day 36

• Percentage of Dose Recovered as Total [14C]-radioactivity in Feces

  Day 1 to Day 36

• Maximum Observed Plasma Concentration (Cmax) of Risdiplam

  Day 1 to Day 36

• Time to Maximum Observed Plasma Concentration of Risdiplam (Tmax)

  Day 1 to Day 36

• Area Under the Plasma Concentration-time Curve from Time 0 to Last Measurable Concentration Time Point (AUC0-last)

  Day 1 to Day 36

• Area Under Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf)

  Day 1 to Day 36

• Apparent Terminal Elimination Half-Life (t1/2)

  Day 1 to Day 36

Secondary Outcomes (2)

• Percentage of Participants with Adverse Events

  Up to 10 weeks

• Percentage of Participants with Laboratory, ECGs, Ophthalmological Assessments, And Vital Signs Abnormalities

  Up to 10 weeks

Study Arms (1)

[^14C]-Risdiplam

EXPERIMENTAL

Participants will be administered with \[\^14C\]-Risdiplam solution orally under fasted conditions on Day 1.

Drug: [^14C]-Risdiplam

Interventions

[^14C]-Risdiplam DRUG

\[\^14C\]-Risdiplam 18 mg oral solution with approximately 0.75 megabecquerel MBq (20 microcuries \[μCi\]) of \[14C\]-labeled Risdiplam.

[^14C]-Risdiplam

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male participants, 35 to 65 years of age (inclusive)
• A body mass index between 18 to 30 kg/m\^2 inclusive
• Agreement to use two methods of contraception, during the treatment period and for at least 4 months after the last dose of study drug. One of the contraceptive methods must be a condom. The second contraceptive method must include one of the following: diaphragm or cervical cap, intra-uterine device or system, or oral, injected or implanted hormonal method of contraception.
• No intention of donating sperm within 4 months of study drug administration
• Able to participate and willing to give written informed consent and to comply with the study requirements and restrictions
• Fluent in the language of the Investigator and study staff and able to communicate with the study staff

You may not qualify if:

• Any condition or disease detected during the medical interview/physical examination that would render the participant unsuitable for the study, place the participant at undue risk or interfere with the ability of the participant to complete the study in the opinion of the Investigator
• History of any clinically significant gastrointestinal, renal, hepatic, broncho- pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder, hypofertility, cancer or cirrhosis
• Participants with any clinically significant eye pathology affecting best-corrected visual acuity, or optic neuritis retinal abnormalities on spectral domain - optical coherence tomography and 7-field fundus color photography as assessed by an ophthalmologist
• History or evidence of (neuro) muscular disorders
• History or evidence of any medical condition potentially altering the absorption, metabolism or elimination of drugs. Surgical history of the gastrointestinal tract affecting gastric motility or altering the gastrointestinal tract
• History or evidence of skin disorders, as assessed by a thorough skin examination of the whole body
• History of malignancy in the past 5 years
• A history of clinically significant hypersensitivity (e.g., drugs, excipients) or allergic reactions
• Participants who, in the Investigator's judgment, pose a suicidal or homicidal risk, or any participant with a history of suicidal or homicidal attempts
• Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to study drug administration
• History or presence of clinically significant ECG abnormalities before study drug administration or cardiovascular disease
• Clinically significant abnormalities in laboratory test results
• Positive results on tests for human immunodeficiency virus (HIV)-1 or HIV-2, hepatitis C virus or hepatitis B virus
• Any suspicion or history of alcohol abuse and/or suspicion of regular consumption of drugs of abuse
• Confirmed systolic blood pressure (SBP) greater than 150 or less than 90 mmHg, and diastolic blood pressure (DBP) greater than 95 or less than 50 mmHg

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Pra International Group B.V

Groningen, 9728 NZ, Netherlands

Location

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  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 26, 2017
• First Posted: January 30, 2017
• Study Start: January 3, 2017
• Primary Completion: February 28, 2017
• Study Completion: February 28, 2017
• Last Updated: October 4, 2018

Record last verified: 2018-10

Locations

NL (1)