Amyotrophic Lateral SclerosisPhase 1NCT02655614
A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis
A Phase 1 study testing GDC-0134, Rabeprazole and Midazolam in people with Amyotrophic Lateral Sclerosis, run by Genentech, Inc. at 10 sites in 3 countries.
Trial summary
This first-in-human, double-blind, placebo-controlled Phase I study will be conducted in participants with amyotrophic lateral sclerosis (ALS) to explore safety, tolerability, and pharmacokinetic (PK) properties of GDC-0134. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- GDC-0134, Rabeprazole and Midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 31 May 2016to 16 Mar 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants with a diagnosis of possible, laboratory-supported probable, probable, or definite ALS according to modified El Escorial criteria
- Upright forced vital capacity of at least 50 percent (%)
- Ability to fast from food for 8 hours prior to dosing and 2 hours after dosing
Who cannot join
- Currently taking riluzole unless on a stable dose for the 3 months prior to Day -1 and without current liver enzyme or liver function abnormalities
- Currently taking edaravone unless after completion of at least the second 14-day drug-treatment period, as long as Day 1 occurs during a drug-free period at least 24 hours after the last edaravone dose and at least 5 days prior to the first dose of the next cycle
- Positive for hepatitis C antibody, hepatitis B surface antigen, or human immunodeficiency virus (HIV) antibody
- Clinically significant thrombocytopenia
- Currently taking nutritional/herbal supplements, except for over-the-counter vitamins that are within Recommended Dietary Allowance (RDA), unless discontinued at least 7 days prior to Day -1, except upon approval of both the investigator and Sponsor
- For participants participating in a designated drug-drug interaction (DDI) cohort in the MAD stage of the study, who require midazolam/caffeine administration: known allergy, religious prohibition, or other condition limiting midazolam or caffeine administration
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United States8 sites
The Emory ALS Clinic
Atlanta, Georgia, 30322
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21205
Massachusetts General Hospital
Boston, Massachusetts, 02114
Mayo Clinic Hospital - Florida
Jacksonville, Florida, 32224
New Orleans Center for Clinical Research
Knoxville, Tennessee, 37920
University of Miami Miller School of Medicine
Miami, Florida, 33136
Wake Research Associates
Raleigh, North Carolina, 27612
Forbes Norris Mda/als Ctr; Research Center
San Francisco, California, 94115
Canada1 site
MUCH - Montreal Neurological Institute & Hospital
Montreal, Quebec, H3A 2B4
About this study
Official title: A Phase I, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Single- and Multiple-Ascending-Dose Study to Determine Initial Safety, Tolerability, and Pharmacokinetics of GDC-0134 in Patients With Amyotrophic Lateral Sclerosis
This first-in-human, double-blind, placebo-controlled Phase I study will be conducted in participants with amyotrophic lateral sclerosis (ALS) to explore safety, tolerability, and pharmacokinetic (PK) properties of GDC-0134. It will include three components: a Single-Ascending-Dose (SAD) stage, a Multiple-Ascending-Dose (MAD) stage, and an Open-Label Safety Expansion (OSE) stage.
- Conditions
- Amyotrophic Lateral Sclerosis
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GDC-0134Drug
GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.
PlaceboDrug
Placebo matching to GDC-0134
RabeprazoleDrug
Rabeprazole 20 mg twice daily orally
MidazolamDrug
2mg of liquid formulation of midazolam orally
CaffeineDrug
100 mg tablet or solution of caffeine orally
| Study group | Role | What they receive |
|---|---|---|
| SAD Stage: GDC-0134 | Experimental | Participants in multiple cohorts and treatment periods will receive single doses of GDC-0134 oral capsules under fed/fasting conditions. To study the effect of proton pump inhibitor (PPI) medication rabeprazole on PK properties of GDC-0134, few participants may receive rabeprazole 20 milligrams (mg). Receives: Drug: GDC-0134; Drug: Rabeprazole |
| SAD Stage: Placebo | Placebo comparator | Participants in multiple cohorts and treatment periods will receive placebo matching to GDC-0134 under fed/fasting conditions. Few participants may receive rabeprazole 20 mg. Receives: Drug: Placebo; Drug: Rabeprazole |
| MAD Stage: GDC-0134 | Experimental | Participants will receive multiple doses of GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. Receives: Drug: GDC-0134; Drug: Midazolam; Drug: Caffeine |
| MAD Stage: Placebo | Placebo comparator | Participants will receive placebo matching to GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. Receives: Drug: Placebo; Drug: Midazolam; Drug: Caffeine |
| Open-Label Safety Expansion (OSE) | Other | Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort. Receives: Drug: GDC-0134 |
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: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Laboratory Abnormalities
Measured: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Vital Signs Abnormalities
Measured: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Measured: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings
Measured: From randomization up to approximately 48 months
Secondary outcomes (14)
Maximum Plasma Concentration (Cmax) of GDC-0134
Measured: From Day 1 up to 28 days after last dose
Time to Maximum Plasma Concentration (tmax) of GDC-0134
Measured: From Day 1 up to 28 days after last dose
Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134
Measured: From Day 1 up to 28 days after last dose
Apparent Clearance (CL/F) of GDC-0134
Measured: From Day 1 up to 28 days after last dose
Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134
Measured: From Day 1 up to 28 days after last dose
Apparent Terminal Half-Life (t1/2) of GDC-0134
Measured: From Day 1 up to 28 days after last dose
PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC
Measured: From Day 1 up to 28 days after last dose
Accumulation Ratio of GDC-0134
Measured: From Day 1 up to 28 days after last dose
Dose Normalized Cmax (Cmax/Dose) of GDC-0134
Measured: From Day 1 up to 28 days after last dose
Dose Normalized AUC (AUC/Dose) of GDC-0134
Measured: From Day 1 up to 28 days after last dose
t1/2 of Midazolam
Measured: From Day -1 up to 28 days after last dose
t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam)
Measured: From Day -1 up to 28 days after last dose
t1/2 of Caffeine
Measured: From Day -1 up to 28 days after last dose
t1/2 of Paraxanthine (Metabolite of Caffeine)
Measured: From Day -1 up to 28 days after last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2016 (estimated)
- Study start31 May 2016
- Primary completion16 Mar 2020
- Study completion16 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The 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
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02655614
- Sponsor's protocol ID
- GN29823
- Other IDs
- 2017-002931-41, 2017
- Status last verified
- Aug 2020
- First submitted
- 7 Jan 2016
- Last updated
- 6 Aug 2020
- Results posted
- No
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Single- and Multiple-Ascending-Dose Study to Determine Initial Safety, Tolerability, and Pharmacokinetics of GDC-0134 in Patients With Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT02655614
- Acronym / sponsor ID
- GN29823
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 31 May 2016 (actual)
- Primary completion
- 16 Mar 2020 (actual)
- Study completion
- 16 Mar 2020 (actual)
- First posted
- 14 Jan 2016 (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.
This first-in-human, double-blind, placebo-controlled Phase I study will be conducted in participants with amyotrophic lateral sclerosis (ALS) to explore safety, tolerability, and pharmacokinetic (PK) properties of GDC-0134. It will include three components: a Single-Ascending-Dose (SAD) stage, a Multiple-Ascending-Dose (MAD) stage, and an Open-Label Safety Expansion (OSE) stage.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| SAD Stage: GDC-0134 | Experimental | Drug: GDC-0134, Drug: RabeprazoleParticipants in multiple cohorts and treatment periods will receive single doses of GDC-0134 oral capsules under fed/fasting conditions. To study the effect of proton pump inhibitor (PPI) medication rabeprazole on PK properties of GDC-0134, few participants may receive rabeprazole 20 milligrams (mg). |
| SAD Stage: Placebo | Placebo comparator | Drug: Placebo, Drug: RabeprazoleParticipants in multiple cohorts and treatment periods will receive placebo matching to GDC-0134 under fed/fasting conditions. Few participants may receive rabeprazole 20 mg. |
| MAD Stage: GDC-0134 | Experimental | Drug: GDC-0134, Drug: Midazolam, Drug: CaffeineParticipants will receive multiple doses of GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. |
| MAD Stage: Placebo | Placebo comparator | Drug: Placebo, Drug: Midazolam, Drug: CaffeineParticipants will receive placebo matching to GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. |
| Open-Label Safety Expansion (OSE) | Other | Drug: GDC-0134Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female participants with a diagnosis of possible, laboratory-supported probable, probable, or definite ALS according to modified El Escorial criteria
- Upright forced vital capacity of at least 50 percent (%)
- Ability to fast from food for 8 hours prior to dosing and 2 hours after dosing
Key exclusion criteria (6 listed)
- Currently taking riluzole unless on a stable dose for the 3 months prior to Day -1 and without current liver enzyme or liver function abnormalities
- Currently taking edaravone unless after completion of at least the second 14-day drug-treatment period, as long as Day 1 occurs during a drug-free period at least 24 hours after the last edaravone dose and at least 5 days prior to the first dose of the next cycle
- Positive for hepatitis C antibody, hepatitis B surface antigen, or human immunodeficiency virus (HIV) antibody
- Clinically significant thrombocytopenia
- Currently taking nutritional/herbal supplements, except for over-the-counter vitamins that are within Recommended Dietary Allowance (RDA), unless discontinued at least 7 days prior to Day -1, except upon approval of both the investigator and Sponsor
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 |
|---|---|---|
| GDC-0134GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period. | Drug | MAD Stage: GDC-0134, Open-Label Safety Expansion (OSE), SAD Stage: GDC-0134 |
| PlaceboPlacebo matching to GDC-0134 | Drug | MAD Stage: Placebo, SAD Stage: Placebo |
| RabeprazoleRabeprazole 20 mg twice daily orally | Drug | SAD Stage: GDC-0134, SAD Stage: Placebo |
| Midazolam2mg of liquid formulation of midazolam orally | Drug | MAD Stage: GDC-0134, MAD Stage: Placebo |
| Caffeine100 mg tablet or solution of caffeine orally | Drug | MAD Stage: GDC-0134, MAD Stage: Placebo |
Primary outcome
Percentage of Participants With Adverse Events (AEs)
Time frame: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Laboratory Abnormalities
Time frame: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Vital Signs Abnormalities
Time frame: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Time frame: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings
Time frame: From randomization up to approximately 48 months
14 secondary outcomes
Maximum Plasma Concentration (Cmax) of GDC-0134
Time frame: From Day 1 up to 28 days after last dose
Time to Maximum Plasma Concentration (tmax) of GDC-0134
Time frame: From Day 1 up to 28 days after last dose
Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134
Time frame: From Day 1 up to 28 days after last dose
Apparent Clearance (CL/F) of GDC-0134
Time frame: From Day 1 up to 28 days after last dose
Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134
Time frame: From Day 1 up to 28 days after last dose
Apparent Terminal Half-Life (t1/2) of GDC-0134
Time frame: From Day 1 up to 28 days after last dose
PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC
Time frame: From Day 1 up to 28 days after last dose
Accumulation Ratio of GDC-0134
Time frame: From Day 1 up to 28 days after last dose
Dose Normalized Cmax (Cmax/Dose) of GDC-0134
Time frame: From Day 1 up to 28 days after last dose
Dose Normalized AUC (AUC/Dose) of GDC-0134
Time frame: From Day 1 up to 28 days after last dose
t1/2 of Midazolam
Time frame: From Day -1 up to 28 days after last dose
t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam)
Time frame: From Day -1 up to 28 days after last dose
t1/2 of Caffeine
Time frame: From Day -1 up to 28 days after last dose
t1/2 of Paraxanthine (Metabolite of Caffeine)
Time frame: From Day -1 up to 28 days after last dose
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 6 Aug 2020.
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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
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GDC-0134, Rabeprazole and Midazolam in people with Amyotrophic Lateral Sclerosis, run by Genentech, Inc. at 10 sites in 3 countries.
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 3 inclusion and 6 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 6 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Canada, 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: From randomization up to approximately 48 months). The study lists 5 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 6 Aug 2020.