Hepatitis CPhase 1NCT02161510
Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Participants With Hepatitis C (MK-2248-002)
A Phase 1 study testing MK-2248 in people with Hepatitis C, run by Merck Sharp & Dohme LLC.
Trial summary
The objective of this study is to identify a safe dose of MK-2248 in participants with Hepatitis C Virus (HCV) that mediates at least a 3 log10 reduction in viral load (VL) from baseline. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C
- What is being tested?
- MK-2248
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- No sites listed yet
- Study dates
- Jul 2014to Apr 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- clinical diagnosis of chronic HCV defined by positive serology for HCV or positive HCV RNA for at least 6 months and detectable HCV RNA in peripheral blood ≥10^5 IU/mL at screening
- Body Mass Index (BMI) ≥18 to <37 kg/m^2
- in good health other than HCV infection with normal laboratory values
Who cannot join
- history of clinically significant and not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic (excepting HCV infection), immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- history of cancer other than adequately treated non-melanomatous skin carcinoma, malignancies which have been successfully treated ≥10 years prior with no recurrence, or cancer that is unlikely to sustain a recurrence for the duration of the trial
- 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
- positive for hepatitis B surface antigen or human immunodeficiency virus
- had major surgery or lost 1 unit of blood within 4 weeks prior to screening
- QTc interval ≥470 msec (males) or ≥480 msec (females)
- received prior treatment with other HCV inhibitors
- clinical or laboratory evidence of decompensated liver disease
About this study
Official title: A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Subjects With Hepatitis C Infection
The objective of this study is to identify a safe dose of MK-2248 in participants with Hepatitis C Virus (HCV) that mediates at least a 3 log10 reduction in viral load (VL) from baseline. It is anticipated that once-daily administration of a safe and well tolerated dose of MK-2248 will reduce VL by at least 3 log10 IU/mL.
Read the detailed description
In this Phase 1b study, the pharmacokinetic (PK), pharmacodynamic (PD), and safety profile of MK-2248 in HCV-infected participants will be evaluated as follows: Part I will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (A, B, C, and D). Part II will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (E, F, G, and H). Part III will assess sequentially ascending MK-2248 doses ranging up to ≤800 mg in 2 panels (I and J). The potential relationship between plasma MK-2248 levels and VL reduction will be determined.
- Conditions
- Hepatitis C
- Being tested
- MK-2248
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-2248Drug
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Part I: MK-2248 200 mg (Panel A) | Experimental | HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. Receives: Drug: MK-2248 |
| Part I: MK-2248 ≤800 mg (Panel B) | Experimental | Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Receives: Drug: MK-2248 |
| Part I: MK-2248 ≤800 mg (Panel C) | Experimental | Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth for 7 days. Receives: Drug: MK-2248 |
| Part I: MK-2248 ≤800 mg (Panel D) | Experimental | Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Receives: Drug: MK-2248 |
| Part II: MK-2248 200 mg (Panel E) | Experimental | HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. Receives: Drug: MK-2248 |
| Part II: MK-2248 ≤800 mg (Panel F) | Experimental | Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Receives: Drug: MK-2248 |
| Part II: MK-2248 ≤800 mg (Panel G) | Experimental | Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Receives: Drug: MK-2248 |
| Part II: MK-2248 ≤800 mg (Panel H) | Experimental | Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Receives: Drug: MK-2248 |
| Part III: MK-2248 ≤800 mg (Panel I) | Experimental | Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Receives: Drug: MK-2248 |
| Part III: MK-2248 ≤800 mg (Panel J) | Experimental | Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Receives: Drug: MK-2248 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum change from baseline in VL
Measured: Up to Day 42
Number of participants experiencing an adverse event (AE)
Measured: Up to Day 42
Number of participants who discontinue from study treatment due to an AE
Measured: Up to Day 7
Secondary outcomes (8)
Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)
Measured: Up to Day 10
Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)
Measured: Up to Day 10
Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)
Measured: Up to Day 10
Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs
Measured: Up to Day 10
Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma
Measured: Up to Day 10
Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma
Measured: Up to Day 10
Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma
Measured: Up to Day 10
Apparent volume of distribution (V/F) of MK-2248 in plasma
Measured: Up to Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2014 (estimated)
- Study startJul 2014
- Primary completionNov 2014
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02161510
- Sponsor's protocol ID
- 2248-002
- Other IDs
- 2014-001494-14, 2014
- Status last verified
- Jun 2015
- First submitted
- 10 Jun 2014
- Last updated
- 8 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2015. 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-2248 in Subjects With Hepatitis C Infection
- ClinicalTrials.gov ID
- NCT02161510
- Acronym / sponsor ID
- 2248-002
- Conditions
- Hepatitis C
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Jul 2014
- Primary completion
- Nov 2014 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 11 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to identify a safe dose of MK-2248 in participants with Hepatitis C Virus (HCV) that mediates at least a 3 log10 reduction in viral load (VL) from baseline. It is anticipated that once-daily administration of a safe and well tolerated dose of MK-2248 will reduce VL by at least 3 log10 IU/mL.
Detailed description
In this Phase 1b study, the pharmacokinetic (PK), pharmacodynamic (PD), and safety profile of MK-2248 in HCV-infected participants will be evaluated as follows: Part I will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (A, B, C, and D). Part II will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (E, F, G, and H). Part III will assess sequentially ascending MK-2248 doses ranging up to ≤800 mg in 2 panels (I and J). The potential relationship between plasma MK-2248 levels and VL reduction will be determined.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Part I: MK-2248 200 mg (Panel A) | Experimental | Drug: MK-2248HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. |
| Part I: MK-2248 ≤800 mg (Panel B) | Experimental | Drug: MK-2248Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. |
| Part I: MK-2248 ≤800 mg (Panel C) | Experimental | Drug: MK-2248Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth for 7 days. |
| Part I: MK-2248 ≤800 mg (Panel D) | Experimental | Drug: MK-2248Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. |
| Part II: MK-2248 200 mg (Panel E) | Experimental | Drug: MK-2248HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. |
| Part II: MK-2248 ≤800 mg (Panel F) | Experimental | Drug: MK-2248Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. |
| Part II: MK-2248 ≤800 mg (Panel G) | Experimental | Drug: MK-2248Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. |
| Part II: MK-2248 ≤800 mg (Panel H) | Experimental | Drug: MK-2248Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. |
| Part III: MK-2248 ≤800 mg (Panel I) | Experimental | Drug: MK-2248Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. |
| Part III: MK-2248 ≤800 mg (Panel J) | Experimental | Drug: MK-2248Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- clinical diagnosis of chronic HCV defined by positive serology for HCV or positive HCV RNA for at least 6 months and detectable HCV RNA in peripheral blood ≥10^5 IU/mL at screening
- Body Mass Index (BMI) ≥18 to <37 kg/m^2
- in good health other than HCV infection with normal laboratory values
Key exclusion criteria (8 listed)
- history of clinically significant and not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic (excepting HCV infection), immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- history of cancer other than adequately treated non-melanomatous skin carcinoma, malignancies which have been successfully treated ≥10 years prior with no recurrence, or cancer that is unlikely to sustain a recurrence for the duration of the trial
- 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
- positive for hepatitis B surface antigen or human immunodeficiency virus
- had major surgery or lost 1 unit of blood within 4 weeks prior to screening
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 |
|---|---|---|
| MK-2248MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days | Drug | Part I: MK-2248 200 mg (Panel A), Part I: MK-2248 ≤800 mg (Panel B), Part I: MK-2248 ≤800 mg (Panel C), Part I: MK-2248 ≤800 mg (Panel D), Part II: MK-2248 200 mg (Panel E), Part II: MK-2248 ≤800 mg (Panel F), Part II: MK-2248 ≤800 mg (Panel G), Part II: MK-2248 ≤800 mg (Panel H), Part III: MK-2248 ≤800 mg (Panel I), Part III: MK-2248 ≤800 mg (Panel J) |
Primary outcome
Maximum change from baseline in VL
Time frame: Up to Day 42
Number of participants experiencing an adverse event (AE)
Time frame: Up to Day 42
Number of participants who discontinue from study treatment due to an AE
Time frame: Up to Day 7
8 secondary outcomes
Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)
Time frame: Up to Day 10
Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)
Time frame: Up to Day 10
Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)
Time frame: Up to Day 10
Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs
Time frame: Up to Day 10
Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma
Time frame: Up to Day 10
Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma
Time frame: Up to Day 10
Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma
Time frame: Up to Day 10
Apparent volume of distribution (V/F) of MK-2248 in plasma
Time frame: Up to Day 10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.
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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 MK-2248 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 3 inclusion and 8 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 8 Jun 2015. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 change from baseline in VL (time frame: Up to Day 42). 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?
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 8 Jun 2015.