Trial Outcomes & Findings for Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function (NCT NCT02412098)

NCT ID: NCT02412098

Last Updated: 2019-07-29

Results Overview

AUCinf was defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

49 participants

Primary outcome timeframe

Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours on Day 1 and approximately the same time in the morning as predose of Day 1 on Days 15, 29, 43, and 57

Results posted on

2019-07-29

Participant Flow

Participants were enrolled at study sites in United States, Romania, Germany, and New Zealand. The first participant was screened on 19 March 2015. The last study visit occurred on 22 April 2016.

91 participants were screened. No participants were enrolled in the severe hepatic impairment (cohort 2) arm.

Participant milestones

Participant milestones
Measure	Moderate Hepatic Impairment (Cohort 1) Participants with moderate hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Mild Hepatic Impairment (Cohort 3) Participants with mild hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Normal Hepatic Function Participants with normal hepatic function received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.
Overall Study STARTED	14	14	21
Overall Study COMPLETED	14	14	21
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Moderate Hepatic Impairment (Cohort 1) n=14 Participants Participants with moderate hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Mild Hepatic Impairment (Cohort 3) n=14 Participants Participants with mild hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Normal Hepatic Function n=21 Participants Participants with normal hepatic function received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Total n=49 Participants Total of all reporting groups
Age, Continuous	56 years STANDARD_DEVIATION 5.3 • n=5 Participants	57 years STANDARD_DEVIATION 8.9 • n=7 Participants	55 years STANDARD_DEVIATION 6.9 • n=5 Participants	56 years STANDARD_DEVIATION 7.0 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants	34 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants	15 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	34 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants	42 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	13 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants	35 Participants n=4 Participants
Region of Enrollment Romania	0 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment Germany	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment New Zealand	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours on Day 1 and approximately the same time in the morning as predose of Day 1 on Days 15, 29, 43, and 57

Population: PK Analysis Set included all enrolled participants who received at least one dose of eleclazine and had at least one evaluable PK concentration value reported by the PK laboratory for the corresponding analyte. Healthy control participants may participate in more than one cohorts.

AUCinf was defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment (Cohort 1) n=14 Participants Participants with moderate hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Mild Hepatic Impairment (Cohort 3) n=14 Participants Participants with mild hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Normal Hepatic Function (Matched Control for Cohort 1) n=14 Participants Normal hepatic function (matched control for Cohort 1) included participants that served as controls for participants with moderate hepatic impairment.	Normal Hepatic Function (Matched Control for Cohort 3) n=14 Participants Normal hepatic function (matched control for Cohort 3) included participants that served as controls for participants with mild hepatic impairment.
PK (Pharmacokinetic) Parameter: AUCinf of Eleclazine	42503.2 h*ng/mL Interval 23983.8 to 75322.7	50064.7 h*ng/mL Interval 31758.4 to 78923.2	57795.9 h*ng/mL Interval 37994.2 to 87917.5	39173.2 h*ng/mL Interval 23050.5 to 66573.2

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours on Day 1 and approximately the same time in the morning as predose of Day 1 on Days 15, 29, 43, and 57

Population: Participants in the PK Analysis Set with available data were analyzed. Healthy control participants may participate in more than one cohorts.

AUCinf was defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment (Cohort 1) n=7 Participants Participants with moderate hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Mild Hepatic Impairment (Cohort 3) n=10 Participants Participants with mild hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Normal Hepatic Function (Matched Control for Cohort 1) n=8 Participants Normal hepatic function (matched control for Cohort 1) included participants that served as controls for participants with moderate hepatic impairment.	Normal Hepatic Function (Matched Control for Cohort 3) n=12 Participants Normal hepatic function (matched control for Cohort 3) included participants that served as controls for participants with mild hepatic impairment.
PK Parameter: AUCinf of GS-623134 (Metabolite of Eleclazine)	1880.0 h*ng/mL Interval 980.5 to 3604.4	1983.2 h*ng/mL Interval 1238.3 to 3176.0	2326.2 h*ng/mL Interval 1497.0 to 3614.9	2697.4 h*ng/mL Interval 2023.1 to 3596.5

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours on Day 1 and approximately the same time in the morning as predose of Day 1 on Days 15, 29, 43, and 57

Population: Participants in the PK Analysis Set were analyzed. Healthy control participants may participate in more than one cohorts.

Cmax was defined as the maximum observed concentration of drug in plasma.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment (Cohort 1) n=14 Participants Participants with moderate hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Mild Hepatic Impairment (Cohort 3) n=14 Participants Participants with mild hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Normal Hepatic Function (Matched Control for Cohort 1) n=14 Participants Normal hepatic function (matched control for Cohort 1) included participants that served as controls for participants with moderate hepatic impairment.	Normal Hepatic Function (Matched Control for Cohort 3) n=14 Participants Normal hepatic function (matched control for Cohort 3) included participants that served as controls for participants with mild hepatic impairment.
PK Parameter: Cmax of Eleclazine	214.9 ng/mL Interval 169.4 to 272.5	338.1 ng/mL Interval 283.6 to 403.1	322.9 ng/mL Interval 279.4 to 373.1	331.3 ng/mL Interval 273.1 to 401.9

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours on Day 1 and approximately the same time in the morning as predose of Day 1 on Days 15, 29, 43, and 57

Population: Participants in the PK Analysis Set with available data were analyzed. Healthy control participants may participate in more than one cohorts.

Cmax was defined as the maximum observed concentration of drug in plasma.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment (Cohort 1) n=11 Participants Participants with moderate hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Mild Hepatic Impairment (Cohort 3) n=13 Participants Participants with mild hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Normal Hepatic Function (Matched Control for Cohort 1) n=14 Participants Normal hepatic function (matched control for Cohort 1) included participants that served as controls for participants with moderate hepatic impairment.	Normal Hepatic Function (Matched Control for Cohort 3) n=14 Participants Normal hepatic function (matched control for Cohort 3) included participants that served as controls for participants with mild hepatic impairment.
PK Parameter: Cmax of GS-623134 (Metabolite of Eleclazine)	4.9 ng/mL Interval 3.2 to 7.7	7.3 ng/mL Interval 4.6 to 11.4	6.5 ng/mL Interval 5.0 to 8.4	10.2 ng/mL Interval 7.0 to 15.0

SECONDARY outcome

Timeframe: First dose date up to 31 days

Population: Safety Analysis Set included all enrolled participants who received at least one dose of study drug.

Treatment-emergent adverse events (AEs) are defined as one or both of the following: * Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug. * Any AEs leading to premature discontinuation of study drug.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment (Cohort 1) n=14 Participants Participants with moderate hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Mild Hepatic Impairment (Cohort 3) n=14 Participants Participants with mild hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Normal Hepatic Function (Matched Control for Cohort 1) n=21 Participants Normal hepatic function (matched control for Cohort 1) included participants that served as controls for participants with moderate hepatic impairment.	Normal Hepatic Function (Matched Control for Cohort 3) Normal hepatic function (matched control for Cohort 3) included participants that served as controls for participants with mild hepatic impairment.
Number of Participants Experiencing Treatment-Emergent Adverse Events	6 Participants	8 Participants	3 Participants	—

SECONDARY outcome

Timeframe: First dose date up to 31 days

Population: Participants in the Safety Analysis Set were analyzed.

Treatment-emergent laboratory abnormalities reported as an adverse event (AE) or serious adverse event (SAE) are presented. Laboratory abnormalities that required medical or surgical intervention or led to study drug interruption, modification, or discontinuation were recorded as an AE or SAE, as applicable, and are reported here. Laboratory abnormalities without clinical significance were not recorded as AEs or SAEs and therefore, are not being reported.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment (Cohort 1) n=14 Participants Participants with moderate hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Mild Hepatic Impairment (Cohort 3) n=14 Participants Participants with mild hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Normal Hepatic Function (Matched Control for Cohort 1) n=21 Participants Normal hepatic function (matched control for Cohort 1) included participants that served as controls for participants with moderate hepatic impairment.	Normal Hepatic Function (Matched Control for Cohort 3) Normal hepatic function (matched control for Cohort 3) included participants that served as controls for participants with mild hepatic impairment.
Number of Participants Experiencing Clinical Laboratory Abnormalities Blood Creatinine Increased	0 Participants	1 Participants	0 Participants	—
Number of Participants Experiencing Clinical Laboratory Abnormalities Gamma-glutamyltransferase Increased	0 Participants	1 Participants	0 Participants	—

Adverse Events

Moderate Hepatic Impairment

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Mild Hepatic Impairment

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Normal Hepatic Function

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Moderate Hepatic Impairment n=14 participants at risk Participants with moderate hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Mild Hepatic Impairment n=14 participants at risk Participants with mild hepatic impairment received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.	Normal Hepatic Function n=21 participants at risk Participants with normal hepatic function received a single dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1.
Cardiac disorders Atrial flutter	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Cardiac disorders Atrioventricular block first degree	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Dry mouth	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
General disorders Chest pain	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
General disorders Oedema peripheral	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Humerus fracture	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Investigations Blood creatinine increased	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Investigations Electrocardiogram PR prolongation	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	4.8% 1/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Tenosynovitis	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Nervous system disorders Dizziness	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	4.8% 1/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Nervous system disorders Headache	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Nervous system disorders Somnolence	21.4% 3/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Renal and urinary disorders Pollakiuria	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	14.3% 2/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	4.8% 1/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash pruritic	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Swelling face	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.	0.00% 0/21 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least one dose of study drug.