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Completed

NCT Number: NCT02633709

A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Risdiplam (RO7034067) Given by Mouth in Healthy Volunteers

The objective of this study is to assess the safety and tolerability of Risdiplam (RO7034067) in healthy people. The study will assess what the body does to Risdiplam (RO7034067) and what Risdiplam (RO7034067) does to the body. Risdiplam (RO7034067) will be given by mouth in gradually increasing doses. The data from this study will help to define the dose to further explore Risdiplam (RO7034067) in patients with Spinal Muscular Atrophy.

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Key information

Conditions

Spinal Muscular Atrophy Central Nervous System Diseases Motor Neuron Disease Muscular Atrophy, Spinal Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Spinal Cord Diseases

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Pra International Group B.V

Groningen, 9728 NZ, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy men, aged 18 to 45 years of age, inclusive
  • Body Mass Index (BMI) of 18 to 30 kilograms/meter square, inclusive

Exclusion criteria

  • History or evidence of any medical condition potentially altering the absorption, metabolism or elimination of drugs
  • History of malignancy in the past 5 years
  • A history of clinically significant hypersensitivity (e.g. drugs, excipients) or allergic reactions
  • Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first study drug administration
  • History or presence of clinically significant electrocardiogram (ECG) abnormalities or cardiovascular disease
  • Clinically significant abnormalities in laboratory test results
  • Confirmed resting pulse rate (PR) greater than 100 or less than 40 bpm
  • Confirmed systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg
  • Positive result on HIV1 and HIV2, hepatitis C (HCV) or hepatitis B (HBV)
  • History of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, ophthalmological, dermatological, hematological or allergic disease, metabolic disorder, hypofertility, cancer or cirrhosis
  • History or evidence of (neuro)muscular disorders
  • Hypersensitivity to itraconazole, to any of the other ingredients, or to any other triazole antifungal
  • Any other known contraindications to itraconazole

Treatment and study plan

Itraconazole

Drug

Itraconazole will be administered as an oral 200 mg dose twice daily from Day 1 to Day 8 in Part 3.

Other names: Sporanox®

Placebo

Other

In Part 1 of the study matching oral placebo will be administered once on Day 1.

Risdiplam

Drug

Single ascending oral doses of Risdiplam will be administered on Day 1 of Part 1. In Part 2 a single dose of Risdiplam will be once administered under fasted and once under fed conditions. In Part 3 a single dose of Risdiplam will be once administered alone (Period 1) and once concomitantly to itraconazole (Period 2).

Other names: RO7034067

Primary outcomes

  1. Percentage of Participants with Adverse Events (AEs)

    Time frame: Parts 1 and 2: Up to 21 days after last dose of study drug. Part 3: Up to 28 days after last dose of study drug.

  2. Percentage of Participants with Laboratory Test Abnormalities

    Time frame: Parts 1 and 2: Up to 21 days after last dose of study drug. Part 3: Up to 28 days after last dose of study drug.

  3. Percentage of Participants with Clinically Significant Changes in Safety Measurements, Including Vital Signs and Electrocardiograms (ECGs)

    Time frame: Parts 1 and 2: Up to 21 days after last dose of study drug. Part 3: Up to 28 days after last dose of study drug.

  4. Percentage of Participants with Clinically Significant Changes in Ophthalmological Assessments

    Time frame: Part 1: Up to 26 weeks; Part 2 (Treatment Period [TP] 1 and 2): Up to 29 weeks; Part 3 (TP 1, 2): Up to 30 weeks

Secondary outcomes

  1. Maximum Observed Plasma Concentration (Cmax)

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  2. Time to Maximum Plasma Concentration (Tmax)

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  3. Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast)

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  4. Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf)

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  5. Area Under the Plasma Concentration-Time Curve up to Time t (AUC0-t)

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  6. Apparent Terminal Half-Life (t1/2)

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  7. Apparent Oral Clearance (CL/F)

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  8. Apparent Oral Volume of Distribution (Vz/F)

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  9. Cumulative Amount Excreted Unchanged into Urine (Ae)

    Time frame: Part 1: Day 1, 2, 3, 4

  10. Renal Clearance (CLR)

    Time frame: Part 1: Day 1, 2, 3, 4

  11. Fraction of Dose Excreted Unchanged Renally (Fe)

    Time frame: Part 1: Day 1, 2, 3, 4

  12. Metabolite-to-Parent Ratio (AUCm/AUCp) Corrected for Molecular Weight for AUCInf, AUClast or AUC0-t

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  13. Change from In Vivo Baseline in Splicing Modifications of SMN mRNAs, Including SMN1, SMN2 FL, and SMNdelta7 mRNA in Blood Ex Vivo

    Time frame: Part 1: Day 1

  14. Change from Baseline in SMN Protein Levels in Blood

    Time frame: Part 1: Day -1, 1, 2, 3, 4, 5, 7

  15. Metabolite-to-Parent Ratio (Cmax_m/Cmax_p) for Cmax, Corrected for Molecular Weight

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  16. Predose Trough Plasma Concentration (Ctrough) of Itraconazole

    Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

  17. Change from Baseline in Splicing Modifications of Survival of Motor Neuron (SMN) Messenger Ribonucleic Acids (mRNAs), Including SMN1, SMN2 FL, and SMNdelta7 mRNA in Blood In Vivo

    Time frame: Part 1: Day -1, 1, 2, 3, 4, 5

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Single-Center, Randomized, Investigator/Subject-Blind, Adaptive Single-Ascending-Dose(SAD), Placebo-Controlled, Parallel Study to Investigate the Safety, Tolerability, Pharmacokinetics (Including the Effect of Food and the Effect of Itraconazole on the Pharmacokinetics of a Single Oral Dose of RO7034067), and Pharmacodynamics of RO7034067 Following Oral Administration in Healthy Subjects

Important dates

Study start
2016
Primary completion
2016
Study completion
2016
First posted
Dec 17, 2015
Registry last updated
Oct 4, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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