Hepatitis C InfectionPhase 1NCT02076100

Safety, Pharmacokinetics, and Pharmacodynamics of Ruzasvir (MK-8408) in Participants With Hepatitis C Infection (MK-8408-003)

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

Completed

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

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Hepatitis C Infection
What is being tested?: Ruzasvir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 22 participants
Where: No sites listed yet
Study dates: 27 Mar 2014to 15 Nov 2015
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
No healthy volunteers
Adult, Older adult

Who may be able to join

Body mass index (BMI) >=18 to<=37 kg/m^2
In general good health, except for HCV infection
Clinical diagnosis of chronic HCV infection exclusively GT3 (Panels A-D) or exclusively GT1a (Panels E-F), or exclusively GT2b (Panels G-H).
Must agree to follow the smoking restrictions defined by the CRU
Must agree to use an acceptable method of contraception during the study and for 90 days after the last dose of ruzasvir

Who cannot join

Clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
History of clinically significant hepatic disease, Gilbert's disease or biliary tract disease
History of cancer (malignancy) with the exception of adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, or successfully-treated malignancies ≥10 years prior to screening
History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
Positive for hepatitis B or human immunodeficiency virus (HIV)
Major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening

Show all 15Show fewer

Participated in another investigational trial within 4 weeks prior to the screening visit
QTc interval >=470 msec (for males) or >= 480 msec (for females)
Unable to refrain from or anticipates use of any medication (prescription and/or non-prescription) or herbal remedies beginning approximately 2 weeks prior to first study drug dose, throughout the trial until the post-trial visit
Consumes >2 glasses of alcoholic beverages per day
Regular user (including "recreational use") of any illicit drugs or history of drug (including alcohol) abuse within approximately 12 months
Evidence or history of chronic hepatitis not caused by HCV
Previous treatment with other HCV NS5A inhibitors such as MK-8742, daclatasvir, or MK-8325
Treatment with other HCV therapies such as the HCV protease
Evidence of advanced or decompensated liver disease; evidence of bridging fibrosis or higher grade fibrosis (Metavir score >=3)

About this study

Official title: A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-8408 in Subjects With Hepatitis C Infection

This is a 3-part study of Ruzasvir (MK-8408) for participants with hepatitis C infection. Successive participants will be enrolled as dose levels are evaluated to find the maximum safe and well tolerated dose of Ruzasvir. Part I will be for participants with hepatitis C virus (HCV) genotype 3 (GT3) and will run first: Part II will be for participants with HCV genotype 1a (GT1a), and Part III will be for participants with HCV genotype 2b (GT2b). Parts II and III may run concurrently. The primary study hypothesis is that a safe and tolerable dose of Ruzasvir that reduces viral load will be found to support further clinical investigation.

Conditions: Hepatitis C Infection
Being tested: Ruzasvir
Medical subject headings: Hepatitis C

What participants receive

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

RuzasvirDrug
Also called MK-8408
Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.

Study groups in NCT02076100
Study group	Role	What they receive
Part I GT3 Participants	Experimental	Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated. Receives: Drug: Ruzasvir
Part II GT1a Participants	Experimental	Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated. Receives: Drug: Ruzasvir
Part III GT2b Participants	Experimental	Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated. Receives: Drug: Ruzasvir

What is being measured

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

Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline
Blood was collected at baseline and on Days 1, 2, 3, 4 and 5 to determine HCV RNA levels. Least squares means (LSM) and confidence intervals (CI) were obtained from an analysis of variance (ANOVA) model with maximum log10 HCV RNA change from baseline as response and a fixed effect for treatment. The primary hypothesis was that the mean change from baseline would be a reduction of ≥3 log10. A positive change from baseline indicates a reduction from baseline in log10 HCV RNA.
Measured: Baseline and up to Day 5
Number of Participants Who Experienced One or More Adverse Events (AEs)
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Measured: Up to 61 days
Number of Participants Who Discontinued Study Drug Due To An AE
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Measured: Up to 5 days

Timeline

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

27 Mar 201415 Nov 2015

First posted3 Mar 2014 (estimated)
Study start27 Mar 2014
Primary completion15 Nov 2015
Study completion15 Nov 2015

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.
Other trials for Hepatitis C InfectionStudies 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: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02076100
Sponsor's protocol ID: 8408-003
Other IDs: 2013-005094-41, MK-8408-003
Status last verified: Dec 2018
First submitted: 27 Feb 2014
Last updated: 24 Dec 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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 Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-8408 in Subjects With Hepatitis C Infection
ClinicalTrials.gov ID: NCT02076100
Acronym / sponsor ID: 8408-003
Conditions: Hepatitis C Infection
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 27 Mar 2014 (actual)
Primary completion: 15 Nov 2015 (actual)
Study completion: 15 Nov 2015 (actual)
First posted: 3 Mar 2014 (estimated)
Results: Posted 28 Nov 2018

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: 3

Arm	Type	Receives
Part I GT3 Participants	Experimental	Drug: RuzasvirParticipants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.
Part II GT1a Participants	Experimental	Drug: RuzasvirParticipants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.
Part III GT2b Participants	Experimental	Drug: RuzasvirParticipants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Body mass index (BMI) >=18 to<=37 kg/m^2
In general good health, except for HCV infection
Clinical diagnosis of chronic HCV infection exclusively GT3 (Panels A-D) or exclusively GT1a (Panels E-F), or exclusively GT2b (Panels G-H).
Must agree to follow the smoking restrictions defined by the CRU
Must agree to use an acceptable method of contraception during the study and for 90 days after the last dose of ruzasvir

Key exclusion criteria (15 listed)

Clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
History of clinically significant hepatic disease, Gilbert's disease or biliary tract disease
History of cancer (malignancy) with the exception of adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, or successfully-treated malignancies ≥10 years prior to screening
History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
Positive for hepatitis B or human immunodeficiency virus (HIV)

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
RuzasvirAlso: MK-8408Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.	Drug	Part I GT3 Participants, Part II GT1a Participants, Part III GT2b Participants

Primary outcome

Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline
Time frame: Baseline and up to Day 5
Blood was collected at baseline and on Days 1, 2, 3, 4 and 5 to determine HCV RNA levels. Least squares means (LSM) and confidence intervals (CI) were obtained from an analysis of variance (ANOVA) model with maximum log10 HCV RNA change from baseline as response and a fixed effect for treatment. The primary hypothesis was that the mean change from baseline would be a reduction of ≥3 log10. A positive change from baseline indicates a reduction from baseline in log10 HCV RNA.
Number of Participants Who Experienced One or More Adverse Events (AEs)
Time frame: Up to 61 days
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Number of Participants Who Discontinued Study Drug Due To An AE
Time frame: Up to 5 days
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Results and safety

Results posted to the registry on 28 Nov 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ruzasvir 10 mg - GT3	3	3
Ruzasvir 30 mg - GT3	3	3
Ruzasvir 60 mg - GT3	3	3
Ruzasvir 120 mg - GT3	3	3
Ruzasvir 10 mg - GT2b	3	3
Ruzasvir 60 mg - GT2b	3	3
Ruzasvir 60 mg - GT1a	4	4

Primary outcome: Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline

Time frame: Baseline and up to Day 5. Least squares mean (90% Confidence Interval). Unit: log10 IU/mL

Measure	Ruzasvir 10 mg - GT3 n = 3	Ruzasvir 30 mg - GT3 n = 3	Ruzasvir 60 mg - GT3 n = 3	Ruzasvir 120 mg - GT3 n = 3	Ruzasvir 10 mg - GT2b n = 3	Ruzasvir 60 mg - GT2b n = 3	Ruzasvir 60 mg - GT1a n = 3	Ruzasvir 60 mg - GT1b n = 1
Value	2.84 (1.94 to 3.74)	3.03 (2.13 to 3.94)	3.36 (2.46 to 4.26)	1.81 (0.90 to 2.71)	3.82 (3.15 to 4.50)	3.62 (2.95 to 4.30)	3.63 (2.46 to 4.81)	3.82 (NA to NA)

Population analysed: Participants who complied with the protocol sufficiently to ensure that generated data would exhibit the effects of treatment, according to the underlying scientific model. Compliance covers considerations such as exposure to treatment, availability of measurements and absence of major protocol violations.

Primary outcome: Number of Participants Who Experienced One or More Adverse Events (AEs)

Time frame: Up to 61 days. Count of participants. Unit: Participants

Measure	Ruzasvir 10 mg - GT3 n = 3	Ruzasvir 30 mg - GT3 n = 3	Ruzasvir 60 mg - GT3 n = 3	Ruzasvir 120 mg - GT3 n = 3	Ruzasvir 10 mg - GT2b n = 3	Ruzasvir 60 mg - GT2b n = 3	Ruzasvir 60 mg - GT1a n = 4
Value	0	0	2	1	2	2	2

Population analysed: All participants who received at least one dose of the investigational drug.

Primary outcome: Number of Participants Who Discontinued Study Drug Due To An AE

Time frame: Up to 5 days. Count of participants. Unit: Participants

Measure	Ruzasvir 10 mg - GT3 n = 3	Ruzasvir 30 mg - GT3 n = 3	Ruzasvir 60 mg - GT3 n = 3	Ruzasvir 120 mg - GT3 n = 3	Ruzasvir 10 mg - GT2b n = 3	Ruzasvir 60 mg - GT2b n = 3	Ruzasvir 60 mg - GT1a n = 4
Value	0	0	0	0	0	0	0

Population analysed: All participants who received at least one dose of the investigational drug.

Adverse events

Time frame: Up to 61 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ruzasvir 10 mg - GT3	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Ruzasvir 30 mg - GT3	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Ruzasvir 60 mg - GT3	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Ruzasvir 120 mg - GT3	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Ruzasvir 10 mg - GT2b	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Ruzasvir 60 mg - GT2b	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Ruzasvir 60 mg - GT1a	0 of 4 (0%)	2 of 4 (50%)	0 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Hepatitis C Infection

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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 Ruzasvir in people with Hepatitis C Infection, 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 5 inclusion and 15 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 24 Dec 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 28 Nov 2018). 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?

Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline (time frame: Baseline and up to Day 5). The study lists 3 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 NCT02076100.

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 24 Dec 2018.