Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2017-002931-41 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GDC-0134 | Drug | GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) | From randomization up to approximately 48 months | |
| Percentage of Participants With Clinically Significant Laboratory Abnormalities | From randomization up to approximately 48 months | |
| Percentage of Participants With Clinically Significant Vital Signs Abnormalities | From randomization up to approximately 48 months | |
| Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | From randomization up to approximately 48 months | |
| Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings | From randomization up to approximately 48 months |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of GDC-0134 | From Day 1 up to 28 days after last dose | |
| Time to Maximum Plasma Concentration (tmax) of GDC-0134 | From Day 1 up to 28 days after last dose | |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Forbes Norris Mda/als Ctr; Research Center | San Francisco | California | 94115 | United States | ||
| Mayo Clinic Hospital - Florida |
Not provided
Not provided
Not provided
Not provided
Not provided
| Open-Label Safety Expansion (OSE) |
| Other |
Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort. |
|
| Placebo | Drug | Placebo matching to GDC-0134 |
|
| Rabeprazole | Drug | Rabeprazole 20 mg twice daily orally |
|
| Midazolam | Drug | 2mg of liquid formulation of midazolam orally |
|
| Caffeine | Drug | 100 mg tablet or solution of caffeine orally |
|
| Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134 |
| From Day 1 up to 28 days after last dose |
| Apparent Clearance (CL/F) of GDC-0134 | From Day 1 up to 28 days after last dose |
| Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134 | From Day 1 up to 28 days after last dose |
| Apparent Terminal Half-Life (t1/2) of GDC-0134 | From Day 1 up to 28 days after last dose |
| PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC | From Day 1 up to 28 days after last dose |
| Accumulation Ratio of GDC-0134 | From Day 1 up to 28 days after last dose |
| Dose Normalized Cmax (Cmax/Dose) of GDC-0134 | From Day 1 up to 28 days after last dose |
| Dose Normalized AUC (AUC/Dose) of GDC-0134 | From Day 1 up to 28 days after last dose |
| t1/2 of Midazolam | From Day -1 up to 28 days after last dose |
| t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam) | From Day -1 up to 28 days after last dose |
| t1/2 of Caffeine | From Day -1 up to 28 days after last dose |
| t1/2 of Paraxanthine (Metabolite of Caffeine) | From Day -1 up to 28 days after last dose |
| Jacksonville |
| Florida |
| 32224 |
| United States |
| University of Miami Miller School of Medicine | Miami | Florida | 33136 | United States |
| The Emory ALS Clinic | Atlanta | Georgia | 30322 | United States |
| Johns Hopkins University School of Medicine | Baltimore | Maryland | 21205 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Wake Research Associates | Raleigh | North Carolina | 27612 | United States |
| New Orleans Center for Clinical Research | Knoxville | Tennessee | 37920 | United States |
| MUCH - Montreal Neurological Institute & Hospital | Montreal | Quebec | H3A 2B4 | Canada |
| UMC Utrecht | Utrecht | 3508 GA | Netherlands |
| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D064750 | Rabeprazole |
| D008874 | Midazolam |
| D002110 | Caffeine |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D014970 | Xanthines |
| D000470 | Alkaloids |
| D011688 | Purinones |
| D011687 | Purines |
Not provided
Not provided