Bioavailability of GDC-0134 and the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Participants

NCT03237741 | Completed Phase 1

• 2 other identifiers: GP397782017-000299-27
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the pharmacokinetics and safety of GDC-0134 in healthy female volunteers of non-childbearing potential. The first part of the study will compare the bioavailability of a prototype capsule of GDC-0134 relative to an existing GDC-0134 reference capsule (Periods 1 and 2). The second part of the study will assess the effect of GDC-0134-in-applesauce preparation under fasting conditions, the effect of low and high fat foods as well as the effect of elevated stomach pH via pre-treatment with rabeprazole, a proton pump inhibitor (PPI), under fasted and high-fat meal conditions (Periods 3 and 4).

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (5)

• Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0134

  The AUC0-inf is calculated in a plot of concentration of drug in blood plasma against time and extrapolated to infinity.

  Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

• Area Under the Plasma Concentration-Time Curve up to Time Tau (AUC0-t) of GDC-0134

  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.

  Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

• Maximum Observed Concentration (Cmax) of GDC-0134

  Cmax is the maximum observed concentration of drug in blood plasma.

  Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

• Time to Maximum Concentration (Tmax) of GDC-0134

  Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.

  Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

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

  Half-life is defined as the time required for the drug plasma concentration to be reduced to half.

  Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

Secondary Outcomes (1)

• Percentage of Participants with Adverse Events

  From baseline until 21 days after the last dose of study drug up to approximately 16 weeks

Study Arms (4)

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.

Drug: Reference capsule GDC-0134; Drug: Prototype capsule GDC-0134; Drug: rabeprazole

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.

Drug: Reference capsule GDC-0134; Drug: Prototype capsule GDC-0134; Drug: rabeprazole

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.

Drug: Reference capsule GDC-0134; Drug: Prototype capsule GDC-0134; Drug: rabeprazole

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.

Drug: Reference capsule GDC-0134; Drug: Prototype capsule GDC-0134; Drug: rabeprazole

Interventions

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.

Treatment Sequence 1: ABC1D1; Treatment Sequence 2: ABC2D2; Treatment Sequence 3: BAC1D1; Treatment Sequence 4: BAC2D2

Prototype capsule GDC-0134 DRUG

Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule.

Treatment Sequence 1: ABC1D1; Treatment Sequence 2: ABC2D2; Treatment Sequence 3: BAC1D1; Treatment Sequence 4: BAC2D2

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.

Treatment Sequence 1: ABC1D1; Treatment Sequence 2: ABC2D2; Treatment Sequence 3: BAC1D1; Treatment Sequence 4: BAC2D2

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 significant findings from medical history, 12-lead echocardiogram (ECG), and vital signs;
• Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the investigator;
• Normal ophthalmology assessment.

You may not qualify if:

• Males and females of childbearing potential;
• Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the investigator;
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator;
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs;
• History of GI bleeding or GI ulcers;
• Any personal or family history of bleeding disorders, and any personal use of drugs known to affect blood clotting within 30 days of dosing;
• Any acute or chronic medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the subject's safe participation in and completion of the study.

Sponsors & Collaborators

• Genentech, Inc.: lead
• Quotient Clinical: collaborator

Study Sites (1)

Quotient Clinical Ltd, Clinical Research Unit

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Rabeprazole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2017
• First Posted: August 2, 2017
• Study Start: August 7, 2017
• Primary Completion: December 14, 2017
• Study Completion: December 14, 2017
• Last Updated: March 1, 2024

Record last verified: 2024-02

Locations

GB (1)