Trial Outcomes & Findings for A Study to Investigate the Effect of RO7049389 on the Pharmacokinetics of Pitavastatin in Healthy Volunteers (NCT NCT03717064)

NCT ID: NCT03717064

Last Updated: 2020-01-10

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 18 participants
• Primary outcome timeframe: Period 1 Day 1
• Results posted on: 2020-01-10

Participant Flow

This study recruited healthy adult participants at one site in the United States.

This study had two periods. Period 1: Participants received a single dose of pitavastatin, followed by a washout period of 7-21 days. Period 2: Participants received a single dose of pitavastatin along with a twice-daily dose of RO7049389.

Participant milestones

Measure	Pitavastatin/RO7049389 Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1 STARTED	18
Period 1 COMPLETED	18
Period 1 NOT COMPLETED	0
Period 2 STARTED	18
Period 2 COMPLETED	17
Period 2 NOT COMPLETED	1

Reasons for withdrawal

Measure	Pitavastatin/RO7049389 Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2 Adverse Event	1

Baseline Characteristics

A Study to Investigate the Effect of RO7049389 on the Pharmacokinetics of Pitavastatin in Healthy Volunteers

Baseline characteristics by cohort

Measure	Pitavastatin/RO7049389 n=18 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Age, Continuous	39.2 Years STANDARD_DEVIATION 14.5 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Period 1 Day 1

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1: Maximum Plasma Concentration (Cmax) of Pitavastatin	23.8 ng/mL Geometric Coefficient of Variation 42.7

PRIMARY outcome

Timeframe: Period 1 Day 1

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin	78.6 h*ng/mL Geometric Coefficient of Variation 41

PRIMARY outcome

Timeframe: Period 1 Day 1

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1: Time to Maximum Concentration (Tmax) of Pitavastatin	1.5 hours (h) Interval 0.5 to 2.0

PRIMARY outcome

Timeframe: Period 1

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1: Apparent Total Clearance (CL/F) of Pitavastatin	25.4 L/h Geometric Coefficient of Variation 39.9

PRIMARY outcome

Timeframe: Period 1 Day 1

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1: Volume of Distribution (V/F) of Pitavastatin	525 Liters (L) Geometric Coefficient of Variation 41.3

PRIMARY outcome

Timeframe: Period 1 Day 1

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1: Elimination Half-Life (T1/2) of Pitavastatin	14.3 h Geometric Coefficient of Variation 32.4

PRIMARY outcome

Timeframe: Period 2 Day 4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: Maximum Plasma Concentration (Cmax) of Pitavastatin	33.5 ng/mL Geometric Coefficient of Variation 52.7

PRIMARY outcome

Timeframe: Period 2 Day 4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin	129 h*ng/mL Geometric Coefficient of Variation 50.7

PRIMARY outcome

Timeframe: Period 2 Day 4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: Time to Maximum Concentration (Tmax) of Pitavastatin	2 h Interval 0.5 to 4.0

PRIMARY outcome

Timeframe: Period 2 Day 4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: Apparent Total Clearance (CL/F) of Pitavastatin	15.6 L/h Geometric Coefficient of Variation 45

PRIMARY outcome

Timeframe: Period 2 Day 4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: Volume of Distribution (V/F) of Pitavastatin	220 L Geometric Coefficient of Variation 59.3

PRIMARY outcome

Timeframe: Period 2 Day 4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: Elimination Half-Life (T1/2) of Pitavastatin	9.78 h Geometric Coefficient of Variation 49

SECONDARY outcome

Timeframe: From the start of Period 1 through safety follow-up (Period 2, Day 34)

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Outcome measures

Measure	Pitavastatin/RO7049389 n=18 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Percentage of Participants With Adverse Events (AEs)	39 Percentage of Participants

SECONDARY outcome

Timeframe: Period 2 Days 3-4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: Cmax of RO7049389 RO7049389	15400 ng/mL Geometric Coefficient of Variation 58.1
Period 2: Cmax of RO7049389 RO7049389 + Pitavastatin	17600 ng/mL Geometric Coefficient of Variation 48.4

SECONDARY outcome

Timeframe: Period 2 Days 3-4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: AUC-tau of RO7049389 RO7049389	62700 h*ng/mL Geometric Coefficient of Variation 92.8
Period 2: AUC-tau of RO7049389 RO7049389 + Pitavastatin	68500 h*ng/mL Geometric Coefficient of Variation 81.8

SECONDARY outcome

Timeframe: Period 1 Day 1

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1: Cmax of Pitavastatin Lactone	14.4 ng/mL Geometric Coefficient of Variation 23.5

SECONDARY outcome

Timeframe: Period 1 Day 1

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1: AUC0-inf of Pitavastatin Lactone	193 h*ng/mL Geometric Coefficient of Variation 27.4

SECONDARY outcome

Timeframe: Period 1 Day 1

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 1: AUC Ratio of Pitavastatin Lactone to Pitavastatin	2.45 Ratio Interval 2.17 to 2.78

SECONDARY outcome

Timeframe: Period 2 Day 4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: Cmax of Pitavastatin Lactone	6.39 ng/mL Geometric Coefficient of Variation 24.4

SECONDARY outcome

Timeframe: Period 2 Day 4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: AUC0-inf of Pitavastatin Lactone	81.7 h*ng/mL Geometric Coefficient of Variation 19.9

SECONDARY outcome

Timeframe: Period 2 Day 4

Outcome measures

Measure	Pitavastatin/RO7049389 n=17 Participants Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Period 2: AUC Ratio of Pitavastatin Lactone to Pitavastatin	0.636 Ratio Interval 0.504 to 0.802

Adverse Events

Pitavastatin/RO7049389

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Pitavastatin/RO7049389 n=18 participants at risk Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days. Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4.
Gastrointestinal disorders Hypoaesthesia oral	5.6% 1/18 • Number of events 1 • From the start of Period 1 through safety follow-up (Period 2, Day 34)
Gastrointestinal disorders Nausea	11.1% 2/18 • Number of events 2 • From the start of Period 1 through safety follow-up (Period 2, Day 34)
Gastrointestinal disorders Vomiting	5.6% 1/18 • Number of events 1 • From the start of Period 1 through safety follow-up (Period 2, Day 34)
General disorders Fatigue	5.6% 1/18 • Number of events 1 • From the start of Period 1 through safety follow-up (Period 2, Day 34)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.6% 1/18 • Number of events 1 • From the start of Period 1 through safety follow-up (Period 2, Day 34)
Nervous system disorders Dizziness	11.1% 2/18 • Number of events 2 • From the start of Period 1 through safety follow-up (Period 2, Day 34)
Nervous system disorders Headache	16.7% 3/18 • Number of events 3 • From the start of Period 1 through safety follow-up (Period 2, Day 34)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.6% 1/18 • Number of events 1 • From the start of Period 1 through safety follow-up (Period 2, Day 34)

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 1-800-821-8590

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