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A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

GDC-0134

Placebo

Rabeprazole

Midazolam

Caffeine

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Other

Arm Label

SAD Stage: GDC-0134

SAD Stage: Placebo

MAD Stage: GDC-0134

MAD Stage: Placebo

Open-Label Safety Expansion (OSE)

Arm Description

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).

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.

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.

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.

Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort.

Outcomes

Primary Outcome Measures

Percentage of Participants With Adverse Events (AEs)

Percentage of Participants With Clinically Significant Laboratory Abnormalities

Percentage of Participants With Clinically Significant Vital Signs Abnormalities

Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings

Secondary Outcome Measures

Maximum Plasma Concentration (Cmax) of GDC-0134

Time to Maximum Plasma Concentration (tmax) of GDC-0134

Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134

Apparent Clearance (CL/F) of GDC-0134

Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134

Apparent Terminal Half-Life (t1/2) of GDC-0134

PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC

Accumulation Ratio of GDC-0134

Dose Normalized Cmax (Cmax/Dose) of GDC-0134

Dose Normalized AUC (AUC/Dose) of GDC-0134

t1/2 of Midazolam

t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam)

t1/2 of Caffeine

t1/2 of Paraxanthine (Metabolite of Caffeine)

Full Information

NCT ID

NCT02655614

First Posted

January 7, 2016

Last Updated

August 4, 2020

Sponsor

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02655614

Brief Title

A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

May 31, 2016 (Actual)

Primary Completion Date

March 16, 2020 (Actual)

Study Completion Date

March 16, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SAD Stage: GDC-0134

Arm Type

Experimental

Arm Description

Arm Title

SAD Stage: Placebo

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

MAD Stage: GDC-0134

Arm Type

Experimental

Arm Description

Arm Title

MAD Stage: Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Open-Label Safety Expansion (OSE)

Arm Type

Other

Arm Description

Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort.

Intervention Type

Drug

Intervention Name(s)

GDC-0134

Intervention Description

GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo matching to GDC-0134

Intervention Type

Drug

Intervention Name(s)

Rabeprazole

Intervention Description

Rabeprazole 20 mg twice daily orally

Intervention Type

Drug

Intervention Name(s)

Midazolam

Intervention Description

2mg of liquid formulation of midazolam orally

Intervention Type

Drug

Intervention Name(s)

Caffeine

Intervention Description

100 mg tablet or solution of caffeine orally

Primary Outcome Measure Information:

Title

Percentage of Participants With Adverse Events (AEs)

Time Frame

From randomization up to approximately 48 months

Title

Percentage of Participants With Clinically Significant Laboratory Abnormalities

Time Frame

From randomization up to approximately 48 months

Title

Percentage of Participants With Clinically Significant Vital Signs Abnormalities

Time Frame

From randomization up to approximately 48 months

Title

Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

Time Frame

From randomization up to approximately 48 months

Title

Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings

Time Frame

From randomization up to approximately 48 months

Secondary Outcome Measure Information:

Title

Maximum Plasma Concentration (Cmax) of GDC-0134

Time Frame