Approval Probability
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Also known as Reference capsule GDC-0134, Reference GDC-0134
GDC-0134 · 2 trials · 1 indication
The AUC0-inf is calculated in a plot of concentration of drug in blood plasma against time and extrapolated to infinity.
The AUC0-t is calculated in a plot of concentration of drug in blood plasma against time and calculated up to the time of the last measurable GDC-0134 concentration.
Cmax is the maximum observed concentration of drug in blood plasma.
Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.
Half-life is defined as the time required for the drug plasma concentration to be reduced to half.
| Arm | Type | Description |
|---|---|---|
| Treatment Sequence 1: ABC1D1 | EXPERIMENTAL | Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days. |
| Treatment Sequence 2: ABC2D2 | EXPERIMENTAL | Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days. |
| Treatment Sequence 3: BAC1D1 | EXPERIMENTAL | Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days. |
| Treatment Sequence 4: BAC2D2 | EXPERIMENTAL | Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days. |
| 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. |
| Open-Label Safety Expansion (OSE) | OTHER | Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort. |
| Name | Type | Description |
|---|---|---|
| Reference capsule GDC-0134 | DRUG | Oral administration of a single dose of 200 milligrams (mg) GDC-0134 reference capsule administered as two 100 mg capsules. |
| Prototype capsule GDC-0134 | DRUG | Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule. |
| rabeprazole | DRUG | Oral administration of 20 mg rabeprazole once daily on Days -3, -2 and -1 as well as on Day 1 two hours prior to each administration of GDC-0134 during Period 4. |
| GDC-0134 | DRUG | GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period. |
| Placebo | DRUG | Placebo matching to GDC-0134 |
| Midazolam | DRUG | 2mg of liquid formulation of midazolam orally |
| Caffeine | DRUG | 100 mg tablet or solution of caffeine orally |
Inclusion Criteria: * Healthy female participants between 30 and 65 years of age, inclusive; * Within body mass index range 18.0 to 35.0 kilograms per square meter (kg/m\^2), inclusive; * Female participants will be of non-childbearing potential; * In good health, determined by no clinically signif...
GDC-0134 is an investigational small molecule being studied for the treatment of amyotrophic lateral sclerosis (ALS), a progressive neurological disease. It has been evaluated in Phase 1 clinical trials in participants with ALS as well as in healthy volunteers. It is not approved for any indication.
GDC-0134 is being developed by Roche Holding AG, which trades under the ticker RHHBY. Roche sponsored the Phase 1 clinical program evaluating the drug in amyotrophic lateral sclerosis and in healthy volunteers.
GDC-0134 is in Phase 1 clinical development. Two Phase 1 trials have been conducted, and both are now completed. The drug remains investigational and has not been approved for marketing in any indication.
GDC-0134 has been studied in two completed Phase 1 trials. NCT02655614 evaluated initial safety, tolerability, and pharmacokinetics in 54 participants with ALS across the United States, Canada, and the Netherlands. NCT03237741 assessed bioavailability and the effects of food and a proton pump inhibitor in 18 healthy female participants in the United Kingdom.
Yes. GDC-0134 is also referred to as Reference capsule GDC-0134 and Reference GDC-0134. These names refer to the same investigational small molecule developed by Roche for amyotrophic lateral sclerosis.
The GDC-0134 Phase 1 program included randomized, double-blind, placebo-controlled trials. NCT02655614 enrolled 54 participants with ALS, and NCT03237741 enrolled 18 healthy female volunteers. Together the two completed trials involved 72 participants.