Trial Outcomes & Findings for Evaluating Fine Needle Aspiration to Measure Hepatic Vaniprevir (MK-7009) Concentrations in Participants With Chronic Hepatitis C (MK-7009-048) (NCT NCT01678131)

Last Updated: 2022-08-26

Results Overview

Liver samples were collected by FNA at 3 of 5 of the following specified postdose timepoints: 3, 12, 24, 48 and 72 hours after a single vaniprevir dose on Day 7. The technical success of the FNA procedure was established for a participant if vaniprevir was detected from at least 2 of the 3 FNA collection timepoints.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

31 participants

Primary outcome timeframe

Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose

Results posted on

2022-08-26

Participant Flow

Participant milestones

Participant milestones
Measure	600 mg Vaniprevir Participants received 600 mg vaniprevir only from Days 1-7; and had postdose liver biopsy from Day 7 up to Day 10 done by Fine Needle Aspiration (FNA) and Core Needle Biopsy (CNB).	300 mg Vaniprevir + PegIFN/RBV Participants received 300 mg vaniprevir from Days 1-7; Pegylated Interferon (Peg-IFN) alpha-2b once weekly, Ribavirin (RBV) twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.	600 mg Vaniprevir + PegIFN/RBV Participants received 600 mg vaniprevir from Days 1-7; Peg-IFN once weekly, RBV twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.
Overall Study STARTED	10	10	11
Overall Study COMPLETED	10	9	9
Overall Study NOT COMPLETED	0	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	600 mg Vaniprevir Participants received 600 mg vaniprevir only from Days 1-7; and had postdose liver biopsy from Day 7 up to Day 10 done by Fine Needle Aspiration (FNA) and Core Needle Biopsy (CNB).	300 mg Vaniprevir + PegIFN/RBV Participants received 300 mg vaniprevir from Days 1-7; Pegylated Interferon (Peg-IFN) alpha-2b once weekly, Ribavirin (RBV) twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.	600 mg Vaniprevir + PegIFN/RBV Participants received 600 mg vaniprevir from Days 1-7; Peg-IFN once weekly, RBV twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.
Overall Study Adverse Event	0	1	0
Overall Study Withdrawal by Subject	0	0	2

Baseline Characteristics

Evaluating Fine Needle Aspiration to Measure Hepatic Vaniprevir (MK-7009) Concentrations in Participants With Chronic Hepatitis C (MK-7009-048)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	600 mg Vaniprevir n=10 Participants Participants received 600 mg vaniprevir only from Days 1-7; and had postdose liver biopsy from Day 7 up to Day 10 done by Fine Needle Aspiration (FNA) and Core Needle Biopsy (CNB).	300 mg Vaniprevir + PegIFN/RBV n=10 Participants Participants received 300 mg vaniprevir from Days 1-7; Pegylated Interferon (Peg-IFN) alpha-2b once weekly, Ribavirin (RBV) twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.	600 mg Vaniprevir + PegIFN/RBV n=11 Participants Participants received 600 mg vaniprevir from Days 1-7; Peg-IFN once weekly, RBV twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.	Total n=31 Participants Total of all reporting groups
Age, Continuous	43.7 Years STANDARD_DEVIATION 10.6 • n=5 Participants	43.9 Years STANDARD_DEVIATION 12.1 • n=7 Participants	38.9 Years STANDARD_DEVIATION 8.0 • n=5 Participants	42.1 Years STANDARD_DEVIATION 10.2 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	25 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose

Population: Participants treated with vaniprevir who had hepatic FNA collected at 3 timepoints. One participant from the 300 mg Vaniprevir + Peg-IFN/RBV treatment group, and one participant from the 600 mg Vaniprevir + Peg-IFN/RBV treatment group discontinued treatment prior to collection of 3 FNAs, and were therefore excluded from the analysis.

Outcome measures

Outcome measures
Measure	600 mg Vaniprevir n=10 Participants Participants received 600 mg vaniprevir only from Days 1-7; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.	300 mg Vaniprevir + PegIFN/RBV n=9 Participants Participants received 300 mg vaniprevir from Days 1-7; Pegylated Interferon (Peg-IFN) alpha-2b once weekly, Ribavirin (RBV) twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.	600 mg Vaniprevir + PegIFN/RBV n=10 Participants Participants received 600 mg vaniprevir from Days 1-7; Peg-IFN once weekly, RBV twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.
Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA	10 Participants	9 Participants	10 Participants

Adverse Events

600 mg Vaniprevir

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

300 mg Vaniprevir + PegIFN/RBV

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

600 mg Vaniprevir + PegIFN/RBV

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	600 mg Vaniprevir n=10 participants at risk Participants received 600 mg vaniprevir only from Days 1-7; and had postdose liver biopsy from Day 7 up to Day 10 done by Fine Needle Aspiration (FNA) and Core Needle Biopsy (CNB).	300 mg Vaniprevir + PegIFN/RBV n=10 participants at risk Participants received 300 mg vaniprevir from Days 1-7; Pegylated Interferon (Peg-IFN) alpha-2b once weekly, Ribavirin (RBV) twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.	600 mg Vaniprevir + PegIFN/RBV n=11 participants at risk Participants received 600 mg vaniprevir from Days 1-7; Peg-IFN once weekly, RBV twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.
General disorders Fever	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	100.0% 10/10 • Number of events 17 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	72.7% 8/11 • Number of events 10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Eye disorders Vision blurred	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	18.2% 2/11 • Number of events 2 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Gastrointestinal disorders Epigastric pain	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Gastrointestinal disorders Loose stools	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/11 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Gastrointestinal disorders Nausea	30.0% 3/10 • Number of events 3 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/11 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Gastrointestinal disorders Vomiting	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
General disorders Fatigue	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 2 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	36.4% 4/11 • Number of events 4 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
General disorders Rigors	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
General disorders Weakness	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/11 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Infections and infestations Oral herpes	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	20.0% 2/10 • Number of events 2 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Investigations Neutrophil count decreased	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Investigations White blood cell count decreased	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	18.2% 2/11 • Number of events 2 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/11 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	20.0% 2/10 • Number of events 2 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	36.4% 4/11 • Number of events 4 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Nervous system disorders Dizziness	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Nervous system disorders Headache	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	20.0% 2/10 • Number of events 2 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	45.5% 5/11 • Number of events 6 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Nervous system disorders Syncope	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Nervous system disorders Tonic convulsion	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Respiratory, thoracic and mediastinal disorders Dry cough	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	9.1% 1/11 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/10 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	10.0% 1/10 • Number of events 1 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)	0.00% 0/11 • up to 14 days after last treatment with vaniprevir (up to approximately Day 21)