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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT03036501

Collaborator

(none)

Enrollment

Location

Arm

1.8

Actual Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: [^14C]-Risdiplam	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 3, 2017

Actual Primary Completion Date :

Feb 28, 2017

Actual Study Completion Date :

Feb 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: [^14C]-Risdiplam Participants will be administered with [^14C]-Risdiplam solution orally under fasted conditions on Day 1.	Drug: [^14C]-Risdiplam [^14C]-Risdiplam 18 mg oral solution with approximately 0.75 megabecquerel MBq (20 microcuries [μCi]) of [14C]-labeled Risdiplam.

Arm

Intervention/Treatment

Experimental: [^14C]-Risdiplam

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

Drug: [^14C]-Risdiplam

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pra International Group B.V	Groningen		Netherlands	9728 NZ

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT03036501

Other Study ID Numbers:

BP39122
2016-003461-26

First Posted:

Jan 30, 2017

Last Update Posted:

Oct 4, 2018

Last Verified:

Oct 1, 2018

Additional relevant MeSH terms:

Risdiplam

Study Results

No Results Posted as of Oct 4, 2018