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

• ClinicalTrials.gov Identifier: NCT03036501
• Recruitment Status: Completed
• First Posted: January 30, 2017
• Last Update Posted: October 4, 2018
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: January 26, 2017
• First Posted Date: January 30, 2017
• Last Update Posted Date: October 4, 2018
• Actual Study Start Date: January 3, 2017
• Actual Primary Completion Date: February 28, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2018)

• Percentage of Dose Recovered as Total [14C]-radioactivity in Urine [ Time Frame: Day 1 to Day 36 ]
• Cumulative Urinary Amount of Total [14C]-Radioactivity in Urine [ Time Frame: Day 1 to Day 36 ]
• Percentage of Dose Recovered as Total [14C]-radioactivity in Feces [ Time Frame: Day 1 to Day 36 ]
• Maximum Observed Plasma Concentration (Cmax) of Risdiplam [ Time Frame: Day 1 to Day 36 ]
• Time to Maximum Observed Plasma Concentration of Risdiplam (Tmax) [ Time Frame: Day 1 to Day 36 ]
• Area Under the Plasma Concentration-time Curve from Time 0 to Last Measurable Concentration Time Point (AUC0-last) [ Time Frame: Day 1 to Day 36 ]
• Area Under Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) [ Time Frame: Day 1 to Day 36 ]
• Apparent Terminal Elimination Half-Life (t1/2) [ Time Frame: Day 1 to Day 36 ]

Original Primary Outcome Measures (submitted: January 26, 2017)

• Percentage of Dose Recovered as Total [14C]-radioactivity in Urine [ Time Frame: Day 1 to Day 36 ]
• Cumulative Urinary Amount of Total [14C]-Radioactivity in Urine [ Time Frame: Day 1 to Day 36 ]
• Percentage of Dose Recovered as Total [14C]-radioactivity in Feces [ Time Frame: Day 1 to Day 36 ]
• Maximum Observed Plasma Concentration (Cmax) of RO7034067 [ Time Frame: Day 1 to Day 36 ]
• Time to Maximum Observed Plasma Concentration of RO7034067 (Tmax) [ Time Frame: Day 1 to Day 36 ]
• Area Under the Plasma Concentration-time Curve from Time 0 to Last Measurable Concentration Time Point (AUC0-last) [ Time Frame: Day 1 to Day 36 ]
• Area Under Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) [ Time Frame: Day 1 to Day 36 ]
• Apparent Terminal Elimination Half-Life (t1/2) [ Time Frame: Day 1 to Day 36 ]

Current Secondary Outcome Measures (submitted: January 26, 2017)

• Percentage of Participants with Adverse Events [ Time Frame: Up to 10 weeks ]
• Percentage of Participants with Laboratory, ECGs, Ophthalmological Assessments, And Vital Signs Abnormalities [ Time Frame: Up to 10 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Investigating the Excretion Balance, Pharmacokinetics and Metabolism of a Single Oral Dose of [14C]-Labeled Risdiplam (RO7034067) in Healthy Male Participants
• Official Title: Open-label Study Investigating the Excretion Balance, Pharmacokinetics and Metabolism of a Single Oral Dose of [14C]-Labeled RO7034067 in Healthy Male Subjects
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Healthy

Intervention

Drug: [^14C]-Risdiplam

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

Study Arms

Experimental: [^14C]-Risdiplam

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

Intervention: Drug: [^14C]-Risdiplam

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 26, 2017): 6
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 28, 2017
• Actual Primary Completion Date: February 28, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Confirmed (based on the average of at least 3 consecutive measurements) resting pulse rate greater than 100 or less than 40 bpm
• Participation in an investigational drug or device study within 90 days prior to screening, as calculated from the day of follow-up from the previous study
• Smokers who regularly smoke more than 10 cigarettes daily or equivalent tobacco- containing products
• Dietary restrictions that would prohibit the consumption of standardized meals
• Use of any prohibited medications and food before study start and during the study
• Participants under judicial supervision, guardianship or curatorship
• Infrequent bowel movements (less than once per 24 hours on average)
• Regular work with ionizing radiation or radioactive material
• Participants who plan to attempt to father children within 4 months after study drug administration

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 35 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03036501
• Other Study ID Numbers: BP39122; 2016-003461-26 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: October 2018