A Study to Determine the Bioavailability of Various Formulations of GDC-0134 in Healthy Female Participants of Non-Childbearing Potential

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03807739
• Collaborator: (none)
• Enrollment: 38
• Locations: 2
• Arms: 2
• Actual Duration (Months): 3.9
• Patients Per Site: 19
• Patients Per Site Per Month: 4.9

Study Details

Study Description

Brief Summary

This is a two-part study to determine the relative bioavailability of two different prototype capsules of GDC-0134 to that of an existing reference capsule of GDC-0134 under both fed and fasted conditions. The study is open to healthy female participants of non-childbearing potential.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: GDC-0134 F09 Formulation; Drug: GDC-0134 F15 Formulation; Drug: GDC-0134 F16 Formulation	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study to Determine the Relative Bioavailability of Various Formulations of GDC-0134 in Healthy Female Subjects of Non-Childbearing Potential
• Actual Study Start Date: Feb 1, 2019
• Actual Primary Completion Date: May 30, 2019
• Actual Study Completion Date: May 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part I: GDC-0134 F16 vs F09 Capsule Formulation In Part 1 participants will receive single doses of either GDC-0134 F16 capsules (prototype) or GDC-0134 F09 capsules (reference) after having consumed a standard meal.	Drug: GDC-0134 F09 Formulation; Participants will receive a single oral dose of GDC-0134 reference capsule F09.; Drug: GDC-0134 F16 Formulation; Participants will receive a single oral dose of GDC-0134 prototype capsule F16.
Experimental: Part II: GDC-0134 F15 vs F09 Capsule Formulation In Part 2, participants will receive a single dose of either GDC-0134 F15 capsules (prototype) or GDC-0134 F09 capsules (reference) after an overnight fast.	Drug: GDC-0134 F09 Formulation; Participants will receive a single oral dose of GDC-0134 reference capsule F09.; Drug: GDC-0134 F15 Formulation; Participants will receive a single oral dose of GDC-0134 prototype capsule F15.

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Concentration (Cmax) of GDC-0134. [The time points at which the outcome measure was assessed were 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 336, 504 hours post-dose.]

2. Area Under the Curve Extrapolated to Infinity (AUCinf) of GDC-0134 [The time points at which the outcome measure was assessed were 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 336, 504 hours post-dose.]

Secondary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs) [From baseline through the end of study (approximately 11 weeks)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

• Body mass index (BMI) range 18.5 to 35 kilograms per square meter (kg/m2)

• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, and vital signs;

• Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the principal investigators (PIs)

• Females of non-childbearing potential only

Exclusion Criteria

• History or clinical manifestation of any significant medical condition as determined by the PI (or designee)

• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the PI (or designee)

• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs

• Use of any prescription medications/products within 14 days prior to Check-in (Day -1) for their first treatment period and during the entire study duration, unless deemed acceptable by the PI

• Use of oral antibiotics within 4 weeks or intravenous antibiotics within 8 weeks prior to the Screening evaluation and during the entire study duration

• Use of any over-the-counter, non-prescription preparations within 14 days prior to Check-in (Day -1) for their first treatment period and during the entire study duration, unless deemed acceptable by the PI

• Use of acid reducing medications (proton pump inhibitors [PPIs], histamine H2-receptor antagonists [H2RAs]) within 14 days prior to Check-in (Day -1) for their first treatment period and during the entire study duration. As an alternative, antacids may be allowed at least 4 hours before or after dose

• Use of any vaccines (including seasonal flu and H1N1 vaccines) within 14 days prior to Check-in (Day -1) for their first treatment period

• Use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day -1) for their first treatment period and during the entire study

• Any acute or chronic condition or any other reason that, in the opinion of the PI, would limit the subject's ability to complete and/or participate in this clinical study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Research Unit - Daytona	Daytona Beach	Florida	United States	32117
2	Covance Research Unit - Dallas	Dallas	Texas	United States	75247

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Dec 19, 2018
• Statistical Analysis Plan - Mar 1, 2019

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT03807739
• Other Study ID Numbers: GP40957
• First Posted: Jan 17, 2019
• Last Update Posted: Aug 31, 2020
• Last Verified: Aug 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Study Results

Participant Flow

Recruitment Details	Screening period: Day -28 to Day 2

Arm/Group Title	Part 1: GDC-0134 F09 vs GDC-0134 F16 Capsule Formulation	Part 1: GDC-0134 F16 vs GDC-0134 F09 Capsule Formulation	Part 2: GDC-0134 F09 vs GDC-0134 F15 Capsule Formulation	Part 2: GDC-0134 F15 vs GDC-0134 F09 Capsule Formulation
Arm/Group Description	In Part 1 participants received single doses of either GDC-0134 F09 or GDC-0134 F16 capsules (prototype) after having consumed a standard meal.	In Part 1, participants received a single dose of either GDC-0134 F16 capsules or GDC-0134 F09 capsules after after having consumed a standard meal.	In Part 2 participants received single doses of either GDC-0134 F09 or GDC-0134 F15 capsules (prototype) in fasting conditions.	In Part 2 participants received single doses of either GDC-0134 F15 or GDC-0134 F09 capsules (prototype) in fasting conditions.
Period Title: Overall Study
STARTED	9	10	9	10
COMPLETED	7	10	9	10
NOT COMPLETED	2	0	0	0

Baseline Characteristics

Arm/Group Title	Part I: GDC-0134 F09 vs GDC-0134 F16 Capsule Formulation	Part 1: GDC-0134 F16 vs GDC-0134 F09 Capsule Formulation	Part 2: GDC-0134 F09 vs GDC-0134 F15 Capsule Formulation	Part 2: GDC-0134 F15 vs GDC-0134 F09 Capsule Formulation	Total
Arm/Group Description	In Part 1 participants received single doses of either GDC-0134 F09 capsules (prototype) or GDC-0134 F16 capsules (reference) after having consumed a standard meal.	In Part 1, participants received a single dose of either GDC-0134 F16 capsules or GDC-0134 F09 capsules after after having consumed a standard meal.	In Part 2 participants received single doses of either GDC-0134 F09 or GDC-0134 F15 capsules (prototype) in fasting conditions.	In Part 2 participants received single doses of either GDC-0134 F15 or GDC-0134 F09 capsules (prototype) in fasting conditions.	Total of all reporting groups
Overall Participants	9	10	9	10	38
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.3 (8.9)	56.5 (4.8)	52.6 (7.2)	58.8 (3.1)	56.1 (6.4)
Sex: Female, Male (Count of Participants)
Female	9 100%	10 100%	9 100%	10 100%	38 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 33.3%	2 20%	3 33.3%	4 40%	12 31.6%
Not Hispanic or Latino	6 66.7%	8 80%	6 66.7%	6 60%	26 68.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 11.1%	3 30%	2 22.2%	2 20%	8 21.1%
White	8 88.9%	7 70%	7 77.8%	8 80%	30 78.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	74.5 (12.5)	68.9 (10.9)	73.4 (15.6)	71.5 (10.0)	72.0 (12.0)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	162.9 (7.6)	161.2 (5.8)	159.1 (6.6)	160.6 (5.0)	160.9 (6.2)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.1 (4.2)	26.7 (5.0)	159.1 (4.4)	27.9 (5.1)	27.8 (4.6)

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Concentration (Cmax) of GDC-0134.
Time Frame	The time points at which the outcome measure was assessed were 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 336, 504 hours post-dose.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part 1 GDC-0134 F16 Capsule Fed	Part 1 GDC-0134 F09 Capsule Fed	Part 2 GDC-0134 F15 Fasted	Part 2 GDC-0134 F09 Capsule Fasted
Arm/Group Description	In Part 1 participants received single doses of GDC-0134 F16 after having consumed a standard meal.	In Part I participants received single doses of GDC-0134 F09 capsules after having consumed a standard meal.	In Part 2, participants received a single dose of GDC-0134 F15 capsules after an overnight fast.	In Part 2, participants received a single dose of GDC-0134 F09 capsules after an overnight fast.
Measure Participants	18	19	19	19
Geometric Mean (Geometric Coefficient of Variation) [uM]	5.56 (85.2)	4.45 (93.7)	2.66 (131.5)	2.68 (140.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1 GDC-0134 F16 Capsule Fed, Part 1 GDC-0134 F09 Capsule Fed
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin 80% - 125%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	1.2471
	Confidence Interval	(2-Sided) 90%; 1.1149 to 1.3951
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 2 GDC-0134 F15 Fasted, Part 2 GDC-0134 F09 Capsule Fasted
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin 80% - 125%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	0.9864
	Confidence Interval	(2-Sided) 90%; 0.8531 to 1.1405
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Time Frame	From baseline through the end of study (approximately 11 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part I: GDC-0134 F09 vs GDC-0134 F16 Capsule Formulation	Part II: GDC-0134 F15 vs F09 Capsule Formulation
Arm/Group Description	In Part 1 participants received single doses of either GDC-0134 F09 capsules (prototype) or GDC-0134 F16 capsules (reference) after having consumed a standard meal.	In Part 2, participants received a single dose of either GDC-0134 F15 capsules (prototype) or GDC-0134 F09 capsules (reference) after an overnight fast.
Measure Participants	19	19
Number [Percentage of Participants]	63.2 702.2%	52.6 526%

3. Primary Outcome

Title	Area Under the Curve Extrapolated to Infinity (AUCinf) of GDC-0134
Time Frame	The time points at which the outcome measure was assessed were 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 336, 504 hours post-dose.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part 1 GDC-0134 F16 Capsule Fed	Part 1 GDC-0134 F09 Capsule Fed	Part 2 GDC-0134 F15 Fasted	Part 2 GDC-0134 F09 Capsule Fasted
Arm/Group Description	In Part 1 participants received single doses of GDC-0134 F16 after having consumed a standard meal.	In Part I participants received single doses of GDC-0134 F09 capsules after having consumed a standard meal.	In Part 2, participants received a single dose of GDC-0134 F15 capsules after an overnight fast.	In Part 2, participants received a single dose of GDC-0134 F09 capsules after an overnight fast.
Measure Participants	18	19	19	19
Geometric Mean (Geometric Coefficient of Variation) [uM.h]	190 (78.7)	154 (94.9)	84.8 (103.4)	85.6 (103.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1 GDC-0134 F16 Capsule Fed, Part 1 GDC-0134 F09 Capsule Fed
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin 80% - 125%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	1.2203
	Confidence Interval	(2-Sided) 90%; 1.1175 to 1.3327
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 2 GDC-0134 F15 Fasted, Part 2 GDC-0134 F09 Capsule Fasted
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin 80% - 125%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	0.9947
	Confidence Interval	(2-Sided) 90%; 0.8266 to 1.1968
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From baseline up to 4 months
Adverse Event Reporting Description	The pre-specified intent of the study was to assess the adverse events in participants receiving GDC-0134, regardless of which formulation was given (e.g., F09 vs F16), therefore, all participants receiving GDC-0134 are combined into a single Arm, for each part.
Arm/Group Title	Part I: GDC-0134 F09 vs GDC-0134 F16 Capsule Formulation		Part II: GDC-0134 F15 vs F09 Capsule Formulation
Arm/Group Description	In Part 1 participants received single doses of either GDC-0134 F09 capsules (prototype) or GDC-0134 F16 capsules (reference) after having consumed a standard meal.		In Part 2, participants received a single dose of either GDC-0134 F15 capsules (prototype) or GDC-0134 F09 capsules (reference) after an overnight fast.
All Cause Mortality
	Part I: GDC-0134 F09 vs GDC-0134 F16 Capsule Formulation		Part II: GDC-0134 F15 vs F09 Capsule Formulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)
Serious Adverse Events
	Part I: GDC-0134 F09 vs GDC-0134 F16 Capsule Formulation		Part II: GDC-0134 F15 vs F09 Capsule Formulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Part I: GDC-0134 F09 vs GDC-0134 F16 Capsule Formulation		Part II: GDC-0134 F15 vs F09 Capsule Formulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/19 (52.6%)		10/19 (52.6%)
Eye disorders
Eye pain	0/19 (0%)	0	1/19 (5.3%)	1
Gastrointestinal disorders
Diarrhoea	1/19 (5.3%)	1	0/19 (0%)	0
Nausea	1/19 (5.3%)	2	4/19 (21.1%)	5
Vomiting	1/19 (5.3%)	1	4/19 (21.1%)	4
General disorders
Vessel puncture site swelling	1/19 (5.3%)	1	0/19 (0%)	0
Fatigue	0/19 (0%)	0	3/19 (15.8%)	3
Asthenia	0/19 (0%)	0	1/19 (5.3%)	1
Infections and infestations
Bronchitis	1/19 (5.3%)	1	0/19 (0%)	0
Investigations
Haemoglobin decreased	2/19 (10.5%)	4	0/19 (0%)	0
Haematocrit decreased	1/19 (5.3%)	1	0/19 (0%)	0
Mean cell volume decreased	1/19 (5.3%)	1	0/19 (0%)	0
Blood creatine phosphokinase increased	0/19 (0%)	0	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/19 (5.3%)	1	0/19 (0%)	0
Joint swelling	1/19 (5.3%)	1	0/19 (0%)	0
Neck pain	1/19 (5.3%)	1	0/19 (0%)	0
Nervous system disorders
Headache	7/19 (36.8%)	9	7/19 (36.8%)	8
Dizziness	1/19 (5.3%)	1	3/19 (15.8%)	3
Paraesthesia	1/19 (5.3%)	1	0/19 (0%)	0
Presyncope	1/19 (5.3%)	1	0/19 (0%)	0
Somnolence	1/19 (5.3%)	1	3/19 (15.8%)	3
Skin and subcutaneous tissue disorders
Dry skin	1/19 (5.3%)	1	0/19 (0%)	0
Photosensitivity reaction	0/19 (0%)	0	1/19 (5.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.