Trial Outcomes & Findings for An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib) (NCT NCT01249118)

NCT ID: NCT01249118

Last Updated: 2017-05-10

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 13 participants
• Primary outcome timeframe: Part 2: 0 hours (Hrs) (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
• Results posted on: 2017-05-10

Participant Flow

The study was divided into two parts. In part 1 of the study, safety of GDC-0973 was evaluated and in part 2 pharmacokinetics (PK) of GDC-0973 was evaluated. All PK outcomes apply only to part 2 of the study while safety applies to part 1 and 2 both.

Participant milestones

Measure	Part 1: GDC-0973 IV Infusion First, Then GDC-0973 Capsules Participants received single dose of GDC-0973 2 milligrams (mg) intravenous (IV) infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. There was a washout period of minimum 10 days after each intervention period.	Part 2: GDC-0973 IV Infusion First, Then GDC-0973 Capsules Participants received single dose of GDC-0973 2 mg IV infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. There was a washout period of minimum 10 days after each intervention period.	Part 2: GDC-0973 Capsules First, Then GDC-0973 IV Infusion Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in first intervention period followed by single dose of GDC-0973 2 mg IV infusion in second intervention period. There was a washout period of minimum 10 days after each intervention period.
First Intervention Period STARTED	2	6	5
First Intervention Period COMPLETED	2	6	5
First Intervention Period NOT COMPLETED	0	0	0
First Washout Period STARTED	2	6	5
First Washout Period COMPLETED	2	5	5
First Washout Period NOT COMPLETED	0	1	0
Second Intervention Period STARTED	2	5	5
Second Intervention Period COMPLETED	2	5	5
Second Intervention Period NOT COMPLETED	0	0	0
Second Washout Period STARTED	2	5	5
Second Washout Period COMPLETED	2	5	5
Second Washout Period NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	Part 1: GDC-0973 IV Infusion First, Then GDC-0973 Capsules Participants received single dose of GDC-0973 2 milligrams (mg) intravenous (IV) infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. There was a washout period of minimum 10 days after each intervention period.	Part 2: GDC-0973 IV Infusion First, Then GDC-0973 Capsules Participants received single dose of GDC-0973 2 mg IV infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. There was a washout period of minimum 10 days after each intervention period.	Part 2: GDC-0973 Capsules First, Then GDC-0973 IV Infusion Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in first intervention period followed by single dose of GDC-0973 2 mg IV infusion in second intervention period. There was a washout period of minimum 10 days after each intervention period.
First Washout Period Physician Decision	0	1	0

Baseline Characteristics

An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib)

Baseline characteristics by cohort

Measure	Entire Study Population n=13 Participants Part 1: Participants received single dose of GDC-0973 2 mg IV infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. There was a washout period of minimum 10 days after each intervention period. Part 2: Participants received single dose of GDC-0973 2 mg IV infusion and GDC-0973 20 mg oral capsules (four 5-mg capsules) in either of the two intervention periods. There was a washout period of minimum 10 days after each intervention period.
Age, Continuous	35 Years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Part 2: 0 hours (Hrs) (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population included participants who were randomized, received study drug, and had at least 1 valid PK parameter.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973	20.5 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 35.6	15.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 26.4

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population.

Cmax(dn) is Cmax divided by dose.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Dose Normalized Cmax [Cmax(dn)] of IV and Oral GDC-0973	10.2 ng/mL/mg Geometric Coefficient of Variation 35.6	0.844 ng/mL/mg Geometric Coefficient of Variation 26.4

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Minimum Observed Plasma Trough Concentration (Cmin) of IV and Oral GDC-0973	0.261 ng/mL Geometric Coefficient of Variation 37.1	0.546 ng/mL Geometric Coefficient of Variation 70.0

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of IV and Oral GDC-0973	0.500 hr Interval 0.5 to 0.567	4.00 hr Interval 2.0 to 8.0

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population.

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of IV and Oral GDC-0973	156 ng*hr/mL Geometric Coefficient of Variation 19.1	688 ng*hr/mL Geometric Coefficient of Variation 28.4

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population.

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). AUC (0-t)dn is AUC (0-t) divided by dose.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Dose Normalized AUC (0-t) [AUC (0-t)dn] of IV and Oral GDC-0973	77.8 ng*hr/mL/mg Geometric Coefficient of Variation 19.1	38.2 ng*hr/mL/mg Geometric Coefficient of Variation 28.4

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population.

AUC (0 - ∞)= Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of IV and Oral GDC-0973	188 ng*hr/mL Geometric Coefficient of Variation 16.2	784 ng*hr/mL Geometric Coefficient of Variation 29.5

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population.

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞)dn is AUC(0 - ∞) divided by dose.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Dose Normalized AUC (0 - ∞) [AUC (0 - ∞)dn] of IV and Oral GDC-0973	93.9 ng*hr/mL/mg Geometric Coefficient of Variation 16.2	43.5 ng*hr/mL/mg Geometric Coefficient of Variation 29.5

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population.

t1/2 is the time measured for the plasma concentration of GDC-0973 to decrease by one half.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Plasma Decay Half-Life (t1/2) of IV and Oral GDC-0973	73.8 hr Geometric Coefficient of Variation 17.1	66.2 hr Geometric Coefficient of Variation 18.2

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population who received IV dose of GDC-0973.

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Systemic Clearance (CL) of IV GDC-0973	10.7 Liter (L)/hr Geometric Coefficient of Variation 16.2	—

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population who received oral dose of GDC-0973.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modelling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Outcome measures

Measure	GDC-0973 2 mg IV n=10 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Apparent Oral Clearance (CL/F) of Oral GDC-0973	23.0 L/hr Geometric Coefficient of Variation 29.5	—

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose of Day 1

Population: Full analysis population who received IV dose of GDC-0973.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Volume of Distribution at Steady State (Vss) of IV GDC-0973	1052 Liter Geometric Coefficient of Variation 28.2	—

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population who received oral dose of GDC-0973.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F is influenced by the fraction absorbed.

Outcome measures

Measure	GDC-0973 2 mg IV n=10 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Apparent Volume of Distribution (Vz/F) of Oral GDC-0973	2197 Liter Geometric Coefficient of Variation 31.9	—

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population who received oral dose of GDC-0973.

Absolute oral bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose. F = [AUC (0-∞), oral multiplied by Dose IV] divided by [AUC (0-∞), IV multiplied by Dose oral]. Absolute oral bioavailability is determined for drugs which are administered orally. IV dose is 100% in systemic circulation (dosed directly) and hence no estimation is required.

Outcome measures

Measure	GDC-0973 2 mg IV n=10 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Absolute Oral Bioavailability (F) of GDC-0973	0.457 Ratio Geometric Coefficient of Variation 25.0	—

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1

Population: Full analysis population who received oral dose of GDC-0973. Here, "number of participants analyzed" signified those participants who were evaluable for this outcome.

MAT is mean time required for the drug to reach the central compartment. MAT was estimated from the mean resident time (MRT) from oral and IV administration. MAT was calculated as MRT last of oral dose minus MRT last of IV dose. MAT is analyzed when drug is administered orally (only for non-IV routes of administration).

Outcome measures

Measure	GDC-0973 2 mg IV n=4 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Mean Absorption Time (MAT)	2.67 hr Geometric Coefficient of Variation 58.0	—

PRIMARY outcome

Timeframe: Part 2: 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose on Day 1

Population: Full analysis population.

The cumulative amount of drug excreted in urine over the entire collection interval of 96 hrs was calculated by adding the Aeu of the intervals 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 hrs where Aeu was calculated by multiplying the urine volume within the collection interval by the associated drug concentration.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Amount of Drug Excreted in the Urine (Aeu) of IV and Oral GDC-0973	0.0761 mg Geometric Coefficient of Variation 22.3	0.379 mg Geometric Coefficient of Variation 33.9

PRIMARY outcome

Timeframe: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1 for plasma; 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose for urine

Population: Full analysis population.

CLR was calculated as Aeu divided by AUC (0 - ∞), where Aeu was amount of drug excreted in urine from time 0 to 96 hrs post-dose and AUC(0 - ∞) was area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity hrs post-dose.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Renal Clearance (CLR) of IV and Oral GDC-0973	0.405 L/hr Geometric Coefficient of Variation 20.1	0.484 L/hr Geometric Coefficient of Variation 22.4

PRIMARY outcome

Timeframe: Part 2: 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose

Population: Full analysis population.

% Excreted is the mean percentage of dose recovery in urine and calculated as: (Aeu divided by dose) multiplied by 100, where Aeu was amount of drug excreted in urine from time 0 to 96 hrs post-dose.

Outcome measures

Measure	GDC-0973 2 mg IV n=11 Participants Participants received single dose of GDC-0973 2 mg IV infusion in either of the intervention periods in part 2 of the study.	GDC-0973 20 mg Oral n=10 Participants Participants received single dose of GDC-0973 20 mg oral capsules (four 5-mg capsule) in either of the intervention periods in part 2 of the study.
Percent of GDC-0973 Excreted in the Urine (% Excreted) for IV and Oral GDC-0973	3.81 Percent dose excreted Geometric Coefficient of Variation 22.3	1.90 Percent dose excreted Geometric Coefficient of Variation 33.9

Adverse Events

GDC-0973 2 mg IV

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

GDC-0973 20 mg Oral

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	GDC-0973 2 mg IV n=13 participants at risk Participants received GDC-0973 2 mg IV infusion in either intervention period in part 1 and part 2 of the study.	GDC-0973 20 mg Oral n=12 participants at risk Participants received GDC-0973 20 mg oral capsules (four 5-mg capsule) in either intervention period in part 1 and part 2 of the study.
Gastrointestinal disorders Nausea	0.00% 0/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	16.7% 2/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Gastrointestinal disorders Abdominal distension	7.7% 1/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	0.00% 0/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Gastrointestinal disorders Vomiting	0.00% 0/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	8.3% 1/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Nervous system disorders Dizziness	0.00% 0/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	16.7% 2/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Nervous system disorders Headache	7.7% 1/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	8.3% 1/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Nervous system disorders Loss of consciousness	0.00% 0/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	8.3% 1/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
General disorders Feeling hot	0.00% 0/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	8.3% 1/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
General disorders Infusion site erythema	7.7% 1/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	0.00% 0/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Eye disorders Visual impairment	7.7% 1/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	0.00% 0/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Infections and infestations Viral upper respiratory tract infection	7.7% 1/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	0.00% 0/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Injury, poisoning and procedural complications Excoriation	0.00% 0/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	8.3% 1/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	8.3% 1/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	8.3% 1/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/13 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.	8.3% 1/12 • Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days) Safety population. One participant discontinued study in first period (Part 2) and did not receive GDC-0973 20 mg oral dose in second period. Therefore, only 12 participants were evaluable for adverse events in this treatment arm.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER