Spinal Muscular AtrophyPhase 1NCT02633709
A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Risdiplam (RO7034067) Given by Mouth in Healthy Volunteers
A Phase 1 study testing Itraconazole and Risdiplam in people with Spinal Muscular Atrophy, run by Hoffmann-La Roche at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- Itraconazole and Risdiplam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteNetherlands
- Study dates
- 7 Jan 2016to 4 Aug 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men, aged 18 to 45 years of age, inclusive
- Body Mass Index (BMI) of 18 to 30 kilograms/meter square, inclusive
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- Itraconazole, Placebo, Risdiplam
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ItraconazoleDrug
Also called Sporanox®
Itraconazole will be administered as an oral 200 mg dose twice daily from Day 1 to Day 8 in Part 3.
PlaceboOther
In Part 1 of the study matching oral placebo will be administered once on Day 1.
RisdiplamDrug
Also called RO7034067
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).
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Single Ascending Dose: Placebo | Placebo comparator | Participants will receive a single dose of matching placebo orally on Day 1 of Part 1. Receives: Other: Placebo |
| Part 1: Single Ascending Dose: Risdiplam | Experimental | Participants will receive a single ascending dose (SAD) of Risdiplam orally on Day 1 of Part 1. Receives: Drug: Risdiplam |
| 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. Receives: Drug: Risdiplam |
| 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. Receives: Drug: Risdiplam |
| 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. Receives: Drug: Itraconazole; Drug: Risdiplam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with Adverse Events (AEs)
Measured: 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
Measured: 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)
Measured: 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
Measured: 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 (17)
Maximum Observed Plasma Concentration (Cmax)
Measured: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Time to Maximum Plasma Concentration (Tmax)
Measured: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast)
Measured: 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)
Measured: 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)
Measured: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Apparent Terminal Half-Life (t1/2)
Measured: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Apparent Oral Clearance (CL/F)
Measured: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Apparent Oral Volume of Distribution (Vz/F)
Measured: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Cumulative Amount Excreted Unchanged into Urine (Ae)
Measured: Part 1: Day 1, 2, 3, 4
Renal Clearance (CLR)
Measured: Part 1: Day 1, 2, 3, 4
Fraction of Dose Excreted Unchanged Renally (Fe)
Measured: Part 1: Day 1, 2, 3, 4
Metabolite-to-Parent Ratio (AUCm/AUCp) Corrected for Molecular Weight for AUCInf, AUClast or AUC0-t
Measured: 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
Measured: Part 1: Day 1
Change from Baseline in SMN Protein Levels in Blood
Measured: Part 1: Day -1, 1, 2, 3, 4, 5, 7
Metabolite-to-Parent Ratio (Cmax_m/Cmax_p) for Cmax, Corrected for Molecular Weight
Measured: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Predose Trough Plasma Concentration (Ctrough) of Itraconazole
Measured: 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
Measured: Part 1: Day -1, 1, 2, 3, 4, 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2015 (estimated)
- Study start7 Jan 2016
- Primary completion4 Aug 2016
- Study completion4 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02633709
- Sponsor's protocol ID
- BP29840
- Other IDs
- 2015-004605-16, 2015
- Status last verified
- Oct 2018
- First submitted
- 15 Dec 2015
- Last updated
- 4 Oct 2018
- Results posted
- No
Publications
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.
PubMed 37148485
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02633709
- Acronym / sponsor ID
- BP29840
- Conditions
- Spinal Muscular Atrophy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 7 Jan 2016 (actual)
- Primary completion
- 4 Aug 2016 (actual)
- Study completion
- 4 Aug 2016 (actual)
- First posted
- 17 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1: Single Ascending Dose: Placebo | Placebo comparator | Other: PlaceboParticipants will receive a single dose of matching placebo orally on Day 1 of Part 1. |
| Part 1: Single Ascending Dose: Risdiplam | Experimental | Drug: RisdiplamParticipants will receive a single ascending dose (SAD) of Risdiplam orally on Day 1 of Part 1. |
| Part 2: Food Effect: Fasted-Fed | Experimental | Drug: RisdiplamThis 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. |
| Part 2: Food Effect: Fed-Fasted | Experimental | Drug: RisdiplamThis 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. |
| Part 3: Itraconazole Interaction | Experimental | Drug: Itraconazole, Drug: RisdiplamIn 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy men, aged 18 to 45 years of age, inclusive
- Body Mass Index (BMI) of 18 to 30 kilograms/meter square, inclusive
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ItraconazoleAlso: Sporanox®Itraconazole will be administered as an oral 200 mg dose twice daily from Day 1 to Day 8 in Part 3. | Drug | Part 3: Itraconazole Interaction |
| PlaceboIn Part 1 of the study matching oral placebo will be administered once on Day 1. | Other | Part 1: Single Ascending Dose: Placebo |
| RisdiplamAlso: RO7034067Single 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). | Drug | Part 1: Single Ascending Dose: Risdiplam, Part 2: Food Effect: Fasted-Fed, Part 2: Food Effect: Fed-Fasted, Part 3: Itraconazole Interaction |
Primary outcome
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.
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.
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.
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
17 secondary outcomes
Maximum Observed Plasma Concentration (Cmax)
Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Time to Maximum Plasma Concentration (Tmax)
Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
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
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
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
Apparent Terminal Half-Life (t1/2)
Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Apparent Oral Clearance (CL/F)
Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Apparent Oral Volume of Distribution (Vz/F)
Time frame: Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28
Cumulative Amount Excreted Unchanged into Urine (Ae)
Time frame: Part 1: Day 1, 2, 3, 4
Renal Clearance (CLR)
Time frame: Part 1: Day 1, 2, 3, 4
Fraction of Dose Excreted Unchanged Renally (Fe)
Time frame: Part 1: Day 1, 2, 3, 4
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
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
Change from Baseline in SMN Protein Levels in Blood
Time frame: Part 1: Day -1, 1, 2, 3, 4, 5, 7
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
Predose Trough Plasma Concentration (Ctrough) of Itraconazole
Time frame: 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
Time frame: Part 1: Day -1, 1, 2, 3, 4, 5
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2018.
- Derived from this study: PubMed 37148485Cleary 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Itraconazole and Risdiplam in people with Spinal Muscular Atrophy, run by Hoffmann-La Roche at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02633709, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2018.