NCT01797536

The Influence of Hepatic Insufficiency on the Pharmacokinetics of Elbasvir (MK-8742) (MK-8742-009)

Completed Phase 1 Results posted Last updated 25 October 2018

What this trial tests

Phase 1 trial testing Elbasvir in Hepatic Insufficiency in 31 participants. Completed in 20 August 2014.

Timeline

6 March 2013

Primary endpoint
20 August 2014

20 August 2014

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	31
Start date	6 March 2013
Primary completion	20 August 2014
Estimated completion	20 August 2014
Sites	2 locations across United States

Drugs / interventions tested

• Elbasvir (ELBASVIR) — full drug profile →

Conditions studied

• Hepatic Insufficiency — all drugs for Hepatic Insufficiency →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 75, any sex, with Hepatic Insufficiency. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Area Under the Curve From 0 to Infinity (AUC0-inf) of Elbasvir Primary · Predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the AUC0-inf of elbasvir.

Group	Value	95% CI
Mild Hepatic Insufficiency	1.56	0.95 – 2.57
Moderate Hepatic Insufficiency	1.86	1.10 – 3.16
Severe Hepatic Insufficiency	2.28	1.34 – 3.87
Healthy Participants	2.58	1.58 – 4.24

Area Under the Curve From 0 to 24 Hours (AUC0-24hr) of Elbasvir Primary · Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, and 24

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 to determine the AUC0-24hr of elbasvir.

Group	Value	95% CI
Mild Hepatic Insufficiency	0.87	0.54 – 1.41
Moderate Hepatic Insufficiency	0.92	0.55 – 1.55
Severe Hepatic Insufficiency	0.92	0.55 – 1.54
Healthy Participants	1.45	0.90 – 2.35

Maximum Concentration (Cmax) of Elbasvir Primary · Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the Cmax of Elbasvir.

Group	Value	95% CI
Mild Hepatic Insufficiency	70.1	42.3 – 116.0
Moderate Hepatic Insufficiency	83.0	50.1 – 137.0
Severe Hepatic Insufficiency	70.7	41.3 – 121.0
Healthy Participants	121.0	73.1 – 200.0

Concentration at 24 Hours (C24) After Dosing Elbasvir Primary · Hour 24

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24, to determine the concentration of elbasvir at Hour 24 was determined.

Group	Value	95% CI
Mild Hepatic Insufficiency	22.9	14.0 – 37.5
Moderate Hepatic Insufficiency	25.9	15.3 – 43.9
Severe Hepatic Insufficiency	29.6	17.4 – 50.1
Healthy Participants	37.7	23.0 – 61.7

Time to Maximum Concentration (Tmax) of Elbasvir Primary · Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the maximum concentration (Cmax) of elbasvir. The time to reach Cmax (Tmax) was determined.

Group	Value	95% CI
Mild Hepatic Insufficiency	3.50	2.00 – 6.00
Moderate Hepatic Insufficiency	3.50	2.00 – 4.00
Severe Hepatic Insufficiency	4.00	3.00 – 4.00
Healthy Participants	3.50	2.00 – 4.00

Apparent Terminal Half-Life (t1/2) of Elbasvir Primary · Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the t1/2 of elbasvir.

Group	Value	95% CI
Mild Hepatic Insufficiency	24.80	± 21.65
Moderate Hepatic Insufficiency	25.39	± 34.24
Severe Hepatic Insufficiency	33.72	± 20.82
Healthy Participants	20.74	± 12.64

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 14 days post-dose (total of 14 days for each panel). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Mild Hepatic Insufficiency

Serious: 0/8 (0%)

Deaths: —

Moderate Hepatic Insufficiency

Serious: 1/11 (9%)

Deaths: —

Severe Hepatic Insufficiency

Serious: 0/7 (0%)

Deaths: —

Healthy Participants

Serious: 0/8 (0%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	Mild Hepatic Insufficiency	Moderate Hepatic Insuffici…	Severe Hepatic Insufficiency	Healthy Participants
Alcohol withdrawal syndrome	Psychiatric disorders	—	—	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Mild Hepatic Insufficiency	Moderate Hepatic Insuffici…	Severe Hepatic Insufficiency	Healthy Participants
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Electrolyte imbalance	Metabolism and nutrition disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—

Most-reported serious reactions: Alcohol withdrawal syndrome.

Data from ClinicalTrials.gov NCT01797536 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the pharmacokinetics (PK) profile of elbasvir (MK-8742) after a single dose to participants with mild, moderate, or severe hepatic insufficiency compared with healthy controls.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.