Muscular Atrophy, SpinalPhase 1NCT04718181
Bioavailability and Bioequivalence of Two Risdiplam Tablets in Healthy Participants
A Phase 1 study testing risdiplam and omeprazole in people with Muscular Atrophy, Spinal, run by Hoffmann-La Roche at 4 sites in United States.
Trial summary
The study is a randomized, single oral dose, crossover study in up to three parts to investigate the relative bioavailability and bioequivalence of two different formulations of risdiplam 5 mg (dispersible tablets) versus the current risdiplam oral solution formulation in healthy male and female participants. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Muscular Atrophy, Spinal
- What is being tested?
- risdiplam and omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Feb 2021to 28 Jan 2023
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- A body mass index (BMI) of 18.0 to 32.0 kg/m2
- Male participants, whose partners are women of childbearing potential (WOCBP) or pregnant, must remain abstinent or use adequate contraception methods (both male participant and non-pregnant WOCBP partner) during the treatment period and until 4 months after the last dose of risdiplam or for pregnant female partners during the treatment period and until 28 days after the last dose of risdiplam. Males must refrain from donating sperm during the treatment period and until 4 months after the last dose of risdiplam.
- Willingness and ability to complete all aspects of the study
- A female subject is eligible to participate if she is a woman of non-childbearing potential (WONCBP)
Who cannot join
- History of any clinically significant gastrointestinal (Gl), renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological, or allergic disease, metabolic disorder, cancer or cirrhosis
- Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study, including but not limited to the following: Any major illness within 1 month before screening or any febrile illness within 1 week prior to screening and up to first study drug administration
- History or evidence of any medical condition potentially altering the absorption, metabolism, or elimination of drugs
- Surgical history of the GI tract affecting gastric motility or altering the GI tract (with the exception of uncomplicated appendectomy and hernia repair; a cholecystectomy is exclusionary)
- History or presence of clinically significant ECG abnormalities (at Screening only) or cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome, family history of sudden death)
- History of malignancy in the past 5 years
Show all 18Show fewer
- Confirmed systolic blood pressure (BP) >140 or <90 mmHg, and diastolic BP >90 or <50 mmHg at Screening only
- Confirmed resting heart rate >100 or <40 beats per minute (bpm) at Screening only
- Clinically significant abnormalities in laboratory test results including hematology, chemistry panel, and urinalysis
- Positive result on human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B virus, or hepatitis C virus (serology) tests at Screening only
- Any suspicion or history of alcohol abuse and/or any history or suspicion of regular consumption/addiction of drugs of abuse within 2 years prior to study drug administration or a positive drug screen test as performed at Screening
- Any consumption of tobacco- or nicotine-containing products from 1 month before Check-in until the end of the study
- Donation of blood or blood products for transfusion over 500 mL within 3 months prior to first study drug administration and for the duration of the study
- Currently enrolled in a clinical study involving another investigational product or in any other type of medical research, or have received the last dose of another investigational product within the last 90 days from clinic check-in (Day -1).
- Use of any prescription (other than hormone replacement therapy) or over-the-counter medications, including herbals and vitamins, within 30 days prior to Check-in
- Any clinically significant history of hypersensitivity or allergic reactions, either spontaneous or following study drug administration, or exposure to food or environmental agents
- History of hypersensitivity to any of the excipients in the formulation of the study drug
- Participants under judicial supervision, guardianship, or curatorship
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Dallas Clinical Research Unit
Dallas, Texas, 75247
Daytona Beach Clinical Rsch Unit
Daytona Beach, Florida, 32117
Covance Clinical Research Unit, Inc
Madison, Wisconsin, 53704
QPS- Springfield
Springfield, Missouri, 65802
About this study
Official title: Risdiplam - A Phase I, Open-Label, Multi-Period Crossover Study to Investigate the Safety, Food Effect, Bioavailability and Bioequivalence of Oral Doses of Two Different Formulations in Healthy Subjects
The study is a randomized, single oral dose, crossover study in up to three parts to investigate the relative bioavailability and bioequivalence of two different formulations of risdiplam 5 mg (dispersible tablets) versus the current risdiplam oral solution formulation in healthy male and female participants. The effect of food on these two dispersible tablets and the current oral solution will be studied, as well as the effect of omeprazole on the dispersible tablets.
Read the detailed description
Part 1 of the study is an exploratory comparison of the relative oral bioavailability of the two dispersible tablets versus risdiplam powder for oral solution as the reference. The effect of food on the bioavailability of the two dispersible tablets will be assessed by comparing fed and fasted states in a five-way crossover manner. It will also be assessed whether antacids (omeprazole) have an impact on the bioavailability of the dispersible tablets in a two-way crossover manner. The food effect on the risdiplam oral solution will also be assessed by comparing fed and fasted states in a two-way crossover manner.
In Part 2, based on the data obtained in Part 1 and provided data support further evaluation, a bioequivalence assessment and a food-effect evaluation will be conducted in two groups with the selected dispersible tablet formulation. Each group will randomly receive, in a four-way crossover, a single dose of risdiplam oral solution 5 mg in both fed and fasted states, and a single dose of the selected dispersible tablet in both fed and fasted states.
In Part 3, provided Part 1 data support further evaluation of the second formulation, the second formulation may be assessed for bioequivalence in the same way as described in Part 2.
Enrollment of the same participant in more than one cohort or group will not be permitted regardless of the study part.
- Conditions
- Muscular Atrophy, Spinal
- Being tested
- risdiplam, omeprazole
- 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.
risdiplamDrug
Also called Evrysdi
Risdiplam will be administered orally at a single dose of 5 mg in different formulations. Dispersible tablet formulations (F21/F22) will be administered as swallowed tablet or as tablet dispersed in water. The powder for constitution to an oral solution will be administered as an oral solution constituted with purified water.
omeprazoleDrug
Also called Non-investigational medicinal product
Omeprazole will be administered orally as a capsule at a dose of 40 mg per day
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Cohort A+B: participants will receive, in a five-period crossover way, a single oral dose of risdiplam oral solution 5 mg in fasted state and thereafter risdiplam/F21 or F22 dispersible tablet 5 mg as tablet in fasted and fed states; tablet dispersed in water in fasted and fed states, with a 14-day wash-out period in between the single-dose administrations.
Cohort C+D: participants will receive, in a two-period fixed sequence design, a single dose of risdiplam/F21 or F22 dispersible tablet 5 mg in fasted state and omeprazole 40 mg once daily for 7 days + a single dose of risdiplam/F21 or F22 dispersible tablet 5 mg in fasted state, on the 7th day of omeprazole. There will be a 14-day wash-out between the two treatment periods.
Cohort E: participants will receive, in a two-period crossover design, a single oral dose of risdiplam oral solution 5 mg in fasted and fed states, with a 14-day wash-out period in between the single-dose administrations. Receives: Drug: risdiplam; Drug: omeprazole |
| Part 2 (optional) | Experimental | Group 1: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F21) as swallowed tablet in both fed and fasted states.
Group 2: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F21) as tablet dispersed in water in both fed and fasted states. Receives: Drug: risdiplam |
| Part 3 (optional) | Experimental | Group 1: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F22) as swallowed tablet in both fed and fasted states.
Group 2: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F22) as tablet dispersed in water in both fed and fasted states. Receives: Drug: risdiplam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Plasma Concentration of Risdiplam in Cohorts A and B
Measured: Day 1 to Day 7 in Periods 1-5
Part 1: Plasma Concentration of Risdiplam in Fed and Fasted States in Cohort E
Measured: Day 1 to Day 7 in Period 1 and Period 2
Part 1: Plasma Concentration of Risdiplam in Cohorts C and D
Measured: Period 1: Day 1 to Day 7; Period 2: Day 1 to Day 13
Parts 2 and 3: Plasma Concentration of Risdiplam
Measured: Day 1 to Day 11 in Periods 1-4
Secondary outcomes (1)
Percentage of Participants with Adverse Events and Serious Adverse Events
Measured: Part 1: up to Day 20 in Periods 1-2, up to Day 14 in Periods 3-5; Parts 2 and 3: up to Day 11 in Periods 1-4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start1 Feb 2021
- Primary completion28 Jan 2023
- Study completion28 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscular Atrophy, SpinalStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 131 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
- NCT04718181
- Sponsor's protocol ID
- BP42066
- Status last verified
- Mar 2023
- First submitted
- 18 Jan 2021
- Last updated
- 13 Mar 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risdiplam - A Phase I, Open-Label, Multi-Period Crossover Study to Investigate the Safety, Food Effect, Bioavailability and Bioequivalence of Oral Doses of Two Different Formulations in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04718181
- Acronym / sponsor ID
- BP42066
- Conditions
- Muscular Atrophy, Spinal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 28 Jan 2023 (actual)
- Study completion
- 28 Jan 2023 (actual)
- First posted
- 22 Jan 2021 (actual)
- 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 study is a randomized, single oral dose, crossover study in up to three parts to investigate the relative bioavailability and bioequivalence of two different formulations of risdiplam 5 mg (dispersible tablets) versus the current risdiplam oral solution formulation in healthy male and female participants. The effect of food on these two dispersible tablets and the current oral solution will be studied, as well as the effect of omeprazole on the dispersible tablets.
Detailed description
Part 1 of the study is an exploratory comparison of the relative oral bioavailability of the two dispersible tablets versus risdiplam powder for oral solution as the reference. The effect of food on the bioavailability of the two dispersible tablets will be assessed by comparing fed and fasted states in a five-way crossover manner. It will also be assessed whether antacids (omeprazole) have an impact on the bioavailability of the dispersible tablets in a two-way crossover manner. The food effect on the risdiplam oral solution will also be assessed by comparing fed and fasted states in a two-way crossover manner.
In Part 2, based on the data obtained in Part 1 and provided data support further evaluation, a bioequivalence assessment and a food-effect evaluation will be conducted in two groups with the selected dispersible tablet formulation. Each group will randomly receive, in a four-way crossover, a single dose of risdiplam oral solution 5 mg in both fed and fasted states, and a single dose of the selected dispersible tablet in both fed and fasted states.
In Part 3, provided Part 1 data support further evaluation of the second formulation, the second formulation may be assessed for bioequivalence in the same way as described in Part 2.
Enrollment of the same participant in more than one cohort or group will not be permitted regardless of the study part.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: risdiplam, Drug: omeprazoleCohort A+B: participants will receive, in a five-period crossover way, a single oral dose of risdiplam oral solution 5 mg in fasted state and thereafter risdiplam/F21 or F22 dispersible tablet 5 mg as tablet in fasted and fed states; tablet dispersed in water in fasted and fed states, with a 14-day wash-out period in between the single-dose administrations. Cohort C+D: participants will receive, in a two-period fixed sequence design, a single dose of risdiplam/F21 or F22 dispersible tablet 5 mg in fasted state and omeprazole 40 mg once daily for 7 days + a single dose of risdiplam/F21 or F22 dispersible tablet 5 mg in fasted state, on the 7th day of omeprazole. There will be a 14-day wash-out between the two treatment periods. Cohort E: participants will receive, in a two-period crossover design, a single oral dose of risdiplam oral solution 5 mg in fasted and fed states, with a 14-day wash-out period in between the single-dose administrations. |
| Part 2 (optional) | Experimental | Drug: risdiplamGroup 1: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F21) as swallowed tablet in both fed and fasted states. Group 2: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F21) as tablet dispersed in water in both fed and fasted states. |
| Part 3 (optional) | Experimental | Drug: risdiplamGroup 1: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F22) as swallowed tablet in both fed and fasted states. Group 2: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F22) as tablet dispersed in water in both fed and fasted states. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- A body mass index (BMI) of 18.0 to 32.0 kg/m2
- Male participants, whose partners are women of childbearing potential (WOCBP) or pregnant, must remain abstinent or use adequate contraception methods (both male participant and non-pregnant WOCBP partner) during the treatment period and until 4 months after the last dose of risdiplam or for pregnant female partners during the treatment period and until 28 days after the last dose of risdiplam. Males must refrain from donating sperm during the treatment period and until 4 months after the last dose of risdiplam.
- Willingness and ability to complete all aspects of the study
- A female subject is eligible to participate if she is a woman of non-childbearing potential (WONCBP)
Key exclusion criteria (18 listed)
- History of any clinically significant gastrointestinal (Gl), renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological, or allergic disease, metabolic disorder, cancer or cirrhosis
- Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study, including but not limited to the following: Any major illness within 1 month before screening or any febrile illness within 1 week prior to screening and up to first study drug administration
- History or evidence of any medical condition potentially altering the absorption, metabolism, or elimination of drugs
- Surgical history of the GI tract affecting gastric motility or altering the GI tract (with the exception of uncomplicated appendectomy and hernia repair; a cholecystectomy is exclusionary)
- History or presence of clinically significant ECG abnormalities (at Screening only) or cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome, family history of sudden death)
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 |
|---|---|---|
| risdiplamAlso: EvrysdiRisdiplam will be administered orally at a single dose of 5 mg in different formulations. Dispersible tablet formulations (F21/F22) will be administered as swallowed tablet or as tablet dispersed in water. The powder for constitution to an oral solution will be administered as an oral solution constituted with purified water. | Drug | Part 1, Part 2 (optional), Part 3 (optional) |
| omeprazoleAlso: Non-investigational medicinal productOmeprazole will be administered orally as a capsule at a dose of 40 mg per day | Drug | Part 1 |
Primary outcome
Part 1: Plasma Concentration of Risdiplam in Cohorts A and B
Time frame: Day 1 to Day 7 in Periods 1-5
Part 1: Plasma Concentration of Risdiplam in Fed and Fasted States in Cohort E
Time frame: Day 1 to Day 7 in Period 1 and Period 2
Part 1: Plasma Concentration of Risdiplam in Cohorts C and D
Time frame: Period 1: Day 1 to Day 7; Period 2: Day 1 to Day 13
Parts 2 and 3: Plasma Concentration of Risdiplam
Time frame: Day 1 to Day 11 in Periods 1-4
1 secondary outcome
Percentage of Participants with Adverse Events and Serious Adverse Events
Time frame: Part 1: up to Day 20 in Periods 1-2, up to Day 14 in Periods 3-5; Parts 2 and 3: up to Day 11 in Periods 1-4
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 13 Mar 2023.
- Individual participant dataSharing planned: No. Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
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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
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing risdiplam and omeprazole in people with Muscular Atrophy, Spinal, run by Hoffmann-La Roche at 4 sites in United States.
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 4 inclusion and 18 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 13 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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. 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?
Part 1: Plasma Concentration of Risdiplam in Cohorts A and B (time frame: Day 1 to Day 7 in Periods 1-5). 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?
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 13 Mar 2023.