Hepatitis CPhase 1NCT01390428

Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172-013)

A Phase 1 study testing Grazoprevir in people with Hepatitis C, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This study will compare the pharmacokinetics (PK) of grazoprevir (MK-5172) when administered to participants with mild, moderate or severe hepatic insufficiency (assessed by the criteria of the Child-Pugh's scale) with the PK of grazoprevir when administered to healthy participants. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Hepatitis C
What is being tested?: Grazoprevir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: No sites listed yet
Study dates: 28 Jul 2011to 12 Sep 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

If female, must be of non-childbearing potential or willing to use at least 2 acceptable methods of contraception from enrollment to 2 weeks after the last dose of study drug
No clinically significant abnormality on electrocardiogram
Hepatic Insufficiency Participants Only:
Other than hepatic insufficiency with features of cirrhosis, is otherwise in good health based on medical history, physical examination, vital signs, and laboratory safety tests
Chronic (>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology
Score on the Child-Pugh scale must range from 5 to 6 (mild hepatic insufficiency) to from 7 to 9 (moderate hepatic insufficiency) to from 10 to 15 (severe hepatic insufficiency)
Matched Healthy Participants Only:
In good health based on medical history, physical examination, vital signs, and laboratory safety tests

Who cannot join

History of any illness that might confound the results of the study or poses an additional risk to the participant
History of clinically significant endocrine, gastrointestinal (other than related to their hepatic impairment), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
Pregnancy
Estimated creatinine clearance of ≤60 mL/min
History of stroke, chronic seizures, or major neurological disorder
History of neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment

Show all 14Show fewer

Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort, green tea, gingko, coenzyme Q, ginseng, echinacea, etc.) or nutritional supplements (e.g., garlic supplements), beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the poststudy visit
Participated in another investigational study within 4 weeks
History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
Hepatic Insufficiency Participants Only:
Has a history of hepatitis C infection by serology, regardless of most recent viral load status.
Matched Healthy Participants Only:
History of any chronic and/or active hepatic disease including elevations of serum transaminases, hepatitis, biliary tract disease, or a history of any significant gastrointestinal surgery.
History of hepatitis C. Participants with a history of self-limited hepatitis A with complete resolution documented at least 6 months prior to entry will be eligible for inclusion

About this study

Official title: An Open-label, 3-Part, Multiple Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172)

Conditions: Hepatitis C
Being tested: Grazoprevir
Medical subject headings: Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GrazoprevirDrug
Part 1: oral morning dose of 200 mg daily for 10 days Part 2: oral morning dose of 100 mg daily for 10 days Part 3: oral morning dose of 50 mg daily for 10 days

Study groups in NCT01390428
Study group	Role	What they receive
Part 1-Mild Hepatic Impairment (HI)	Experimental	Participants with mild hepatic impairment will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study. Receives: Drug: Grazoprevir
Part 1-Healthy Matched to Mild HI	Experimental	Healthy participants will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study. Receives: Drug: Grazoprevir
Part 2-Moderate HI	Experimental	Participants with moderate hepatic impairment will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study. Receives: Drug: Grazoprevir
Part 2-Healthy Matched to Moderate HI	Experimental	Healthy participants will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study. Receives: Drug: Grazoprevir
Part 3-Severe HI	Experimental	Participants with severe hepatic impairment will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study. Receives: Drug: Grazoprevir
Part 3-Healthy Matched to Severe HI	Experimental	Healthy participants will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study. Receives: Drug: Grazoprevir

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma AUC0-24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Measured: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Maximum Concentration (Cmax) of Grazoprevir
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Cmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Measured: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Time to Peak Concentration (Tmax) of Grazoprevir
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Tmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Measured: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI
Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Measured: Day 1 at 24 hours postdose
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI
Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Measured: Day 1 at 24 hours postdose
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10
Blood samples were collected at 24 hours post-dose on Day 10 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Measured: Days 10 at 24 hours postdose
Apparent Terminal Half-life (t1/2) of Grazoprevir
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Day 10 in order to determine the plasma t1/2 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Measured: Day 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jul 201112 Sep 2014

First posted11 Jul 2011 (estimated)
Study start28 Jul 2011
Primary completion5 Sep 2014
Study completion12 Sep 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatitis CStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01390428
Sponsor's protocol ID: 5172-013
Status last verified: Aug 2018
First submitted: 7 Jul 2011
Last updated: 14 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Caro L, Wenning L, Guo Z, Fraser IP, Fandozzi C, Talaty J, Panebianco D, Ho M, Uemura N, Reitmann C, Angus P, Gane E, Marbury T, Smith WB, Iwamoto M, Butterton JR, Yeh WW. Effect of Hepatic Impairment on the Pharmacokinetics of Grazoprevir, a Hepatitis C Virus Protease Inhibitor. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e00813-17. doi: 10.1128/AAC.00813-17. Print 2017 Dec.
PubMed 28947470

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Hepatitis C trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, 3-Part, Multiple Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172)
ClinicalTrials.gov ID: NCT01390428
Acronym / sponsor ID: 5172-013
Conditions: Hepatitis C
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 28 Jul 2011 (actual)
Primary completion: 5 Sep 2014 (actual)
Study completion: 12 Sep 2014 (actual)
First posted: 11 Jul 2011 (estimated)
Results: Posted 4 Mar 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Part 1-Mild Hepatic Impairment (HI)	Experimental	Drug: GrazoprevirParticipants with mild hepatic impairment will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.
Part 1-Healthy Matched to Mild HI	Experimental	Drug: GrazoprevirHealthy participants will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.
Part 2-Moderate HI	Experimental	Drug: GrazoprevirParticipants with moderate hepatic impairment will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.
Part 2-Healthy Matched to Moderate HI	Experimental	Drug: GrazoprevirHealthy participants will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.
Part 3-Severe HI	Experimental	Drug: GrazoprevirParticipants with severe hepatic impairment will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Part 3-Healthy Matched to Severe HI	Experimental	Drug: GrazoprevirHealthy participants will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

If female, must be of non-childbearing potential or willing to use at least 2 acceptable methods of contraception from enrollment to 2 weeks after the last dose of study drug
No clinically significant abnormality on electrocardiogram
Other than hepatic insufficiency with features of cirrhosis, is otherwise in good health based on medical history, physical examination, vital signs, and laboratory safety tests
Chronic (>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology
Score on the Child-Pugh scale must range from 5 to 6 (mild hepatic insufficiency) to from 7 to 9 (moderate hepatic insufficiency) to from 10 to 15 (severe hepatic insufficiency)

Key exclusion criteria (14 listed)

History of any illness that might confound the results of the study or poses an additional risk to the participant
History of clinically significant endocrine, gastrointestinal (other than related to their hepatic impairment), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
Pregnancy
Estimated creatinine clearance of ≤60 mL/min
History of stroke, chronic seizures, or major neurological disorder

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GrazoprevirPart 1: oral morning dose of 200 mg daily for 10 days Part 2: oral morning dose of 100 mg daily for 10 days Part 3: oral morning dose of 50 mg daily for 10 days	Drug	Part 1-Healthy Matched to Mild HI, Part 1-Mild Hepatic Impairment (HI), Part 2-Healthy Matched to Moderate HI, Part 2-Moderate HI, Part 3-Healthy Matched to Severe HI, Part 3-Severe HI

Primary outcome

Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir
Time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma AUC0-24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Maximum Concentration (Cmax) of Grazoprevir
Time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Cmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Time to Peak Concentration (Tmax) of Grazoprevir
Time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Tmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI
Time frame: Day 1 at 24 hours postdose
Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI
Time frame: Day 1 at 24 hours postdose
Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10
Time frame: Days 10 at 24 hours postdose
Blood samples were collected at 24 hours post-dose on Day 10 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Apparent Terminal Half-life (t1/2) of Grazoprevir
Time frame: Day 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Day 10 in order to determine the plasma t1/2 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.

Results and safety

Results posted to the registry on 4 Mar 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1-Mild Hepatic Impairment (HI)	8	8
Part 1-Healthy Matched to Mild HI	8	8
Part 2-Moderate HI	9	8
Part 2-Healthy Matched to Moderate HI	9	9
Part 3-Severe HI	8	7
Part 3-Healthy Matched to Severe HI	8	8

Primary outcome: Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir

Time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. Geometric mean (95% Confidence Interval). Unit: uM*hr

Measure	Part 1-Mild HI n = 8	Part 1-Healthy Matched to Mild HI n = 8	Part 2-Moderate HI n = 8	Part 2-Healthy Matched to Moderate HI n = 8	Part 3-Severe HI n = 8	Part 3-Healthy Matched to Severe HI n = 8
Day 1	1.71 (1.10 to 2.65)	1.42 (0.912 to 2.20)	1.61 (0.791 to 3.29)	0.321 (0.157 to 0.655)	1.17 (0.541 to 2.55)	0.0592 (0.0273 to 0.129)
Day 10	6.20 (4.19 to 9.18)	3.74 (2.53 to 5.54)	4.21 (2.48 to 7.14)	0.874 (0.515 to 1.48)	3.00 (1.71 to 5.26)	0.257 (0.146 to 0.451)

Part 1-Mild HI vs Part 1-Healthy Matched to Mild HI: Geometric Least Squares Mean Ratio (GMR): 1.21 (90% CI 0.73 to 2.01)
Part 1-Mild HI vs Part 1-Healthy Matched to Mild HI: GMR: 1.66 (90% CI 1.05 to 2.61)
Part 2-Moderate HI vs Part 2-Healthy Matched to Moderate HI: GMR: 5.03 (90% CI 2.19 to 11.56)

Population analysed: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.

Primary outcome: Maximum Concentration (Cmax) of Grazoprevir

Time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. Geometric mean (95% Confidence Interval). Unit: uM

Measure	Part 1-Mild HI n = 8	Part 1-Healthy Matched to Mild HI n = 8	Part 2-Moderate HI n = 8	Part 2-Healthy Matched to Moderate HI n = 8	Part 3-Severe HI n = 8	Part 3-Healthy Matched to Severe HI n = 8
Day 1	0.257 (0.121 to 0.545)	0.305 (0.144 to 0.646)	0.433 (0.184 to 1.07)	0.0580 (0.0242 to 0.139)	0.238 (0.107 to 0.531)	0.0157 (0.00705 to 0.0350)
Day 10	1.40 (0.903 to 2.17)	1.02 (0.658 to 1.58)	0.631 (0.334 to 1.19)	0.106 (0.0559 to 0.199)	0.396 (0.203 to 0.774)	0.0304 (0.0156 to 0.0595)

Part 1-Mild HI vs Part 1-Healthy Matched to Mild HI: GMR: 0.84 (90% CI 0.35 to 2.01)
Part 1-Mild HI vs Part 1-Healthy Matched to Mild HI: GMR: 1.37 (90% CI 0.83 to 2.27)
Part 2-Moderate HI vs Part 2-Healthy Matched to Moderate HI: GMR: 7.64 (90% CI 2.74 to 21.27)

Population analysed: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.

Primary outcome: Time to Peak Concentration (Tmax) of Grazoprevir

Time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. Median (Full Range). Unit: hr.

Measure	Part 1-Mild HI n = 8	Part 1-Healthy Matched to Mild HI n = 8	Part 2-Moderate HI n = 8	Part 2-Healthy Matched to Moderate HI n = 8	Part 3-Severe HI n = 8	Part 3-Healthy Matched to Severe HI n = 8
Day 1	3.50 (1.00 to 12.00)	2.50 (1.00 to 4.00)	2.00 (1.50 to 4.00)	1.75 (1.00 to 4.00)	1.75 (1.00 to 3.00)	1.50 (1.00 to 4.00)
Day 10	3.00 (2.00 to 4.00)	3.01 (1.5 to 4.00)	3.00 (1.50 to 8.00)	2.00 (1.00 to 6.00)	1.75 (0.50 to 4.00)	1.00 (0.50 to 3.00)

Population analysed: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.

Primary outcome: Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI

Time frame: Day 1 at 24 hours postdose. Geometric mean (95% Confidence Interval). Unit: nM

Measure	Part 1-Mild HI n = 8	Part 1-Healthy Matched to Mild HI n = 8	Part 2-Moderate HI n = 8	Part 2-Healthy Matched to Moderate HI n = 8	Part 3-Severe HI n = 0	Part 3-Healthy Matched to Severe HI n = 0
Value	21.4 (18.2 to 25.2)	11.5 (9.8 to 13.5)	17.7 (8.73 to 35.8)	5.90 (2.92 to 11.9)	–	–

Part 1-Mild HI vs Part 1-Healthy Matched to Mild HI: GMR: 1.86 (90% CI 1.54 to 2.24)
Part 2-Moderate HI vs Part 2-Healthy Matched to Moderate HI: GMR: 2.99 (90% CI 1.31 to 6.82)

Population analysed: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants with Severe HI and Matched Healthy to Severe HI are absent because they had a different Measure Type and Method of Dispersion

Adverse events

Time frame: 14 days after last dose (up to Day 24). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1-Mild HI	0 of 8 (0%)	8 of 8 (100%)	Not reported
Part 1-Healthy Matched to Mild HI	0 of 8 (0%)	5 of 8 (62.5%)	Not reported
Part 2-Moderate HI	0 of 9 (0%)	4 of 9 (44.4%)	Not reported
Part 2-Healthy Matched to Moderate HI	0 of 9 (0%)	4 of 9 (44.4%)	Not reported
Part 3-Severe HI	1 of 8 (12.5%)	4 of 8 (50%)	Not reported
Part 3-Healthy Matched to Severe HI	0 of 8 (0%)	3 of 8 (37.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28947470Caro L, Wenning L, Guo Z, Fraser IP, Fandozzi C, Talaty J, Panebianco D, Ho M, Uemura N, Reitmann C, Angus P, Gane E, Marbury T, Smith WB, Iwamoto M, Butterton JR, Yeh WW. Effect of Hepatic Impairment on the Pharmacokinetics of Grazoprevir, a Hepatitis C Virus Protease Inhibitor. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e00813-17. doi: 10.1128/AAC.00813-17. Print 2017 Dec.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Grazoprevir in people with Hepatitis C, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir (time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01390428, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2018.