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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-004605-16 | EudraCT Number |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Single Ascending Dose: Placebo | Placebo Comparator | Participants will receive a single dose of matching placebo orally on Day 1 of Part 1. |
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| Part 1: Single Ascending Dose: Risdiplam | Experimental | Participants will receive a single ascending dose (SAD) of Risdiplam orally on Day 1 of Part 1. |
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| Part 2: Food Effect: Fasted-Fed | Experimental | This arm consists of two periods. In Period 1 participants will receive one oral dose of Risdiplam in the fasted state on Day 1. In Period 2 participants will receive one oral dose of Risdiplam in the fed state on Day 1. |
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| Part 2: Food Effect: Fed-Fasted | Experimental | This arm consists of two periods. In Period 1 participants will receive one oral dose of Risdiplam in the fed state on Day 1. In Period 2 participants will receive one oral dose of Risdiplam in the fasted state on Day 1. |
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| Part 3: Itraconazole Interaction | Experimental | In Period 1 a single oral dose of Risdiplam will be administered. After a wash-out period in Period 2 participants will be administered oral doses of itraconazole twice daily from Day 1 to Day 8. On Day 4 participants will receive a single oral dose of Risdiplam in the fed state in combination with itraconazole. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Itraconazole | Drug | Itraconazole will be administered as an oral 200 mg dose twice daily from Day 1 to Day 8 in Part 3. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Adverse Events (AEs) | 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. | |
| Percentage of Participants with Laboratory Test Abnormalities | 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. | |
| Percentage of Participants with Clinically Significant Changes in Safety Measurements, Including Vital Signs and Electrocardiograms (ECGs) | 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. | |
| Percentage of Participants with Clinically Significant Changes in Ophthalmological Assessments | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 | |
| Time to Maximum Plasma Concentration (Tmax) | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pra International Group B.V | Groningen | 9728 NZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37148485 | Derived | Cleary Y, Kletzl H, Grimsey P, Heinig K, Ogungbenro K, Silber Baumann HE, Frey N, Aarons L, Galetin A, Gertz M. Estimation of FMO3 Ontogeny by Mechanistic Population Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug-Drug Interactions in Children. Clin Pharmacokinet. 2023 Jun;62(6):891-904. doi: 10.1007/s40262-023-01241-7. Epub 2023 May 6. |
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| 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). |
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| Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) |
| Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 |
| Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 |
| Area Under the Plasma Concentration-Time Curve up to Time t (AUC0-t) | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 |
| Apparent Terminal Half-Life (t1/2) | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 |
| Apparent Oral Clearance (CL/F) | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 |
| Apparent Oral Volume of Distribution (Vz/F) | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 |
| Cumulative Amount Excreted Unchanged into Urine (Ae) | Part 1: Day 1, 2, 3, 4 |
| Renal Clearance (CLR) | Part 1: Day 1, 2, 3, 4 |
| Fraction of Dose Excreted Unchanged Renally (Fe) | Part 1: Day 1, 2, 3, 4 |
| Metabolite-to-Parent Ratio (AUCm/AUCp) Corrected for Molecular Weight for AUCInf, AUClast or AUC0-t | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 |
| Change from In Vivo Baseline in Splicing Modifications of SMN mRNAs, Including SMN1, SMN2 FL, and SMNdelta7 mRNA in Blood Ex Vivo | Part 1: Day 1 |
| Change from Baseline in SMN Protein Levels in Blood | Part 1: Day -1, 1, 2, 3, 4, 5, 7 |
| Metabolite-to-Parent Ratio (Cmax_m/Cmax_p) for Cmax, Corrected for Molecular Weight | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 |
| Predose Trough Plasma Concentration (Ctrough) of Itraconazole | Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28 |
| 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 | Part 1: Day -1, 1, 2, 3, 4, 5 |
| ID | Term |
|---|---|
| D009134 | Muscular Atrophy, Spinal |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
| D019636 | Neurodegenerative Diseases |
| D009468 | Neuromuscular Diseases |
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| ID | Term |
|---|---|
| D017964 | Itraconazole |
| C000629884 | Risdiplam |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010879 | Piperazines |
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