HCV (Genotype 1)Phase 1NCT01250366
Study of the Safety & PK of INX-08189 in Chronically-infected HCV, Treatment-naïve Subjects
A Phase 1 study testing INX-08189 and Ribavirin in people with HCV (Genotype 1), run by Bristol-Myers Squibb at 4 sites in 2 countries.
Trial summary
The purpose of this study is to determine the Safety and Pharmacokinetics of Multiple Ascending Oral Doses of INX-08189 in Chronically-infected Genotype 1 HCV, Treatment-naïve Subjects. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HCV (Genotype 1)
- What is being tested?
- INX-08189 and Ribavirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Oct 2010to Jun 2011
- 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
- At the screening visit (Visit 1), subjects will meet the following criteria:
- Males \& females, 18 - 65 years of age inclusive(BMI of at least 18kg/m2 not exceeding 36kg/m2);
- Diagnosis of chronic HCV by 1 previous PCR result prior to screening, with a positive HCV viral load of at least 100,000IU/ml at screening measured by quantitative PCR;
- HCV genotype 1 per central lab testing report;
- HCV treatment-naïve (defined as no prior treatment with interferon, pegylated interferon, ribavirin, or any HCV direct acting anti-viral drugs);
- Liver biopsy consistent with chronic HCV infection but non-cirrhotic as judged by a pathologist (Knodell < 3, Metavir <2, Ishak <4, or Batts \& Ludwig <2) within the last 2 years \& before Visit 2 (biopsy can be done within screening period);
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- Negative urine drug screen for drugs of abuse at screening and Study Day -1 (methadone use allowed);
- Females will have a negative serum βHCG pregnancy test at screening \& negative urine dipstick pregnancy test upon entry to clinical unit on Study Day -1;
- Agreement by both females of childbearing potential \& males(who have not been surgically sterilized) to practice an acceptable method of birth control. Surgical sterilization of either female or male partner must have occurred at least 6 month prior to first dose \& females must be post-menopausal for 2 years to be considered of non-child-bearing potential. Acceptable contraceptive methods include 1 of the following: Oral \& implantable hormonal contraceptives by female at least 3 months prior to the 1st dose of Study Drug, IUD in place at least 6 months prior to first dose, barrier methods either diaphragm or condom with spermicide. (Abstinence is not an acceptable method of birth control, subjects who indicate sexual inactivity must agree to utilize birth control in the event of sexual activity);
- Willing \& able to complete all study visits and procedures, \& able to communicate with the investigator \& other personnel;
- Signed informed consent form (ICF) executed prior to protocol screening assessments
Who cannot join
- At the screening visit subjects will not meet any of the following criteria:
- Advanced liver disease, cirrhosis, or with signs of decompensated liver disease such as variceal bleeding, ascites, hepatic encephalopathy, active jaundice (total bilirubin > 2, or other evidence of decompensated liver disease;
- Co-infection with HBV or HIV (positive test for HBsAg or anti-HIV Ab);
- Acute cardiac ischemia, unstable heart disease or clinically symptomatic cardiac abnormalities apparent on ECG \& PE, or a QTcB interval at Visit 1 of ≥ to 450ms by Bazette's correction, or personal or family history of Torsades de pointes;
- Use of the following medications concurrently or within the 30 days prior to Screening associated with QT prolongation: macrolides, antiarrhythmic agents, azoles, fluoroquinolones, \& tricyclic anti-depressants (methadone use allowed);
- Use of immunosuppressive or immune-modulating agents (including corticosteroids \& immunosuppressive agents) or presence of an immunologically-mediated autoimmune disease (other than asthma) or history of organ transplantation (inhaled steroids for asthma \& topical steroid for minor skin conditions allowed);
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- Use of strong CYP3A4-inhibiting protease inhibitors (specifically atazanavir, indinavir, nelfinavir, saquinavir, \& ritonavir), strong CYP3A4 inhibitors (specifically clarithromycin, itraconazole, ketoconazole, nefazodone, telithromycin), or strong CYP3A4 inducers (specifically rifampin, efavirenz, etravirine, phenobarbital, phenytoin, \& carbamazepine);
- Absolute NEUT count of <1800 cells/mm3 (or < 1500 cells/mm3 for African Americans), or platelet count <130,000 cells/mm3, or hemoglobin <11g/dl for women and <13g/dl for men;
- A history of abnormal thyroid function not adequately controlled (defined as TSH levels < 0.8 x LLN or > 1.2 x the ULN);
- Serum creatinine concentration > 1.5 times the upper limit of normal, or albumin < 3g/dl;
- Presence or history of severe, or uncontrolled, or hospitalization-requiring psychiatric disease including severe depression, suicide attempts or any severity of psychosis;
- Any malignancy within the last 5 years other than treated cervical carcinoma in situ or treated basal cell carcinoma with no more than 20% risk of recurrence within 2 years;
- Alcohol abuse (investigator assessment) within the past 2 years or an alcohol use pattern that will interfere with the study conduct;
- Drug abuse (investigator assessment)within the last 6 months with exception of methadone;
- Current lactation or breastfeeding;
- Major surgery within 30 days prior Visit 1;
- Participation in another clinical trial of an investigational drug or device within 6 months prior to visit 1;
- Donation of blood or plasma within 30 days prior to Visit 1
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
Study site
Los Angeles, California
Study site
Plymouth, Minnesota
Study site
San Antonio, Texas
About this study
Official title: A Multi-center, Sequential-cohort, Placebo-controlled, 7-day Treatment Period Study of the Safety and Pharmacokinetics of Multiple Ascending Oral Doses of INX-08189 in Chronically-infected Genotype 1 HCV, Treatment-naïve Subjects
The purpose of this study is to determine the Safety and Pharmacokinetics of Multiple Ascending Oral Doses of INX-08189 in Chronically-infected Genotype 1 HCV, Treatment-naïve Subjects.
Read the detailed description
This is a multi-center, sequential-cohort, double-blind, placebo-controlled, multiple ascending dose, 7-day treatment study in chronically-infected genotype 1 HCV, treatment-naïve subjects.
Primary Objectives include:
Safety
- to evaluate the safety of ascending oral doses of INX-08189 given once a day for seven (7) days in chronically-infected genotype 1 HCV, treatment-naïve subjects
Pharmacokinetic
- to characterize the pharmacokinetic (PK) profile of multiple ascending oral doses of INX-08189 in chronically-infected genotype 1 HCV, treatment-naïve subjects
Pharmacodynamic
- to evaluate the relationship between the metrics of the reduction from baseline in serum HCV RNA and PK parameters of INX-08189 and the metabolite INX-08032
Efficacy
- to measure the maximal reduction in plasma HCV RNA by ascending oral dose level of INX-08189 given once a day for seven (7) days in chronically-infected genotype 1 HCV, treatment-naïve subjects
- Conditions
- HCV (Genotype 1)
- Being tested
- INX-08189, Placebo matching with INX-08189, Ribavirin
- Keywords
- Safety and Pharmacokinetics
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INX-08189Drug
Capsules, Oral, 9 mg, Once Daily, 7 Days
INX-08189Drug
Capsule, Oral, 25 mg, Once Daily, 7 days
INX-08189Drug
Capsules, Oral, 50 mg, Single Dose, 1 day
INX-08189Drug
Capsules, Oral, 9 mg, Once daily, 6 days
INX-08189Drug
Capsules, Oral, 50 mg, Once daily, 7 days
INX-08189Drug
Capsules, Oral, 9 mg, Once daily, 7 days
INX-08189Drug
Capsules, Oral, 100 mg, Once daily, 7 days
Placebo matching with INX-08189Drug
Capsules, Oral, 0 mg, Once daily, 7 days
RibavirinDrug
Capsules, Oral, 1000 or 1200 mg daily (delivered in weight-adjusted am/pm divided dose), 7 days
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: INX-08189 (9 mg) or Placebo | Experimental | Not described Receives: Drug: INX-08189; Drug: Placebo matching with INX-08189 |
| Arm 2: INX-08189 (25 mg) or Placebo | Experimental | Not described Receives: Drug: INX-08189; Drug: Placebo matching with INX-08189 |
| Arm 3: INX-08189 (50 mg + 9 mg) or Placebo | Experimental | Not described Receives: Drug: INX-08189; Drug: Placebo matching with INX-08189 |
| Arm 4: INX-08189 (50 mg) or Placebo | Experimental | Not described Receives: Drug: INX-08189; Drug: Placebo matching with INX-08189 |
| Arm 5: INX-08189 (9 mg) or Placebo + Ribavirin | Experimental | Not described Receives: Drug: INX-08189; Drug: Placebo matching with INX-08189; Drug: Ribavirin |
| Arm 6: INX-08189 (25 mg) or Placebo + Ribavirin | Experimental | Not described Receives: Drug: INX-08189; Drug: Placebo matching with INX-08189; Drug: Ribavirin |
| Arm 7: INX-08189 (100 mg) or Placebo | Experimental | Not described Receives: Drug: INX-08189; Drug: Placebo matching with INX-08189 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety will be evaluated in an integrated way on the basis of the Adverse Event profiles, changes in laboratory values (serum chemistry, hematology and urinalysis), ECG data, and vital signs, viral resistance testing and results of Physical Exams.
Measured: periodically over 14 days
PK parameters following administration of INX-08189 will be determined using concentration data obtained via the assay of INX-08189 and INX-08032 in plasma, and the analysis of INX-08032 in urine
Measured: periodically over 14 days
The primary efficacy outcome is the maximum change from baseline in HCV RNA following 7 days of dosing.
Measured: 7 days
Secondary outcomes (1)
Secondary efficacy outcome measures include the change in HCV RNA over time during the seven days of dosing and during the follow-up period thereafter. Additionally, viral load changes will be compared across the two genotypes 1a and 1b.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2010 (estimated)
- Study startOct 2010
- Primary completionMar 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HCV (Genotype 1)Studies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe 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
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01250366
- Sponsor's protocol ID
- AI472-002
- Other IDs
- INH-189-002
- Status last verified
- Jul 2012
- First submitted
- 22 Nov 2010
- Last updated
- 12 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Sequential-cohort, Placebo-controlled, 7-day Treatment Period Study of the Safety and Pharmacokinetics of Multiple Ascending Oral Doses of INX-08189 in Chronically-infected Genotype 1 HCV, Treatment-naïve Subjects
- ClinicalTrials.gov ID
- NCT01250366
- Acronym / sponsor ID
- AI472-002
- Conditions
- HCV (Genotype 1)
- Keywords
- Safety and Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 30 Nov 2010 (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 purpose of this study is to determine the Safety and Pharmacokinetics of Multiple Ascending Oral Doses of INX-08189 in Chronically-infected Genotype 1 HCV, Treatment-naïve Subjects.
Detailed description
This is a multi-center, sequential-cohort, double-blind, placebo-controlled, multiple ascending dose, 7-day treatment study in chronically-infected genotype 1 HCV, treatment-naïve subjects.
Primary Objectives include:
Safety
- to evaluate the safety of ascending oral doses of INX-08189 given once a day for seven (7) days in chronically-infected genotype 1 HCV, treatment-naïve subjects
Pharmacokinetic
- to characterize the pharmacokinetic (PK) profile of multiple ascending oral doses of INX-08189 in chronically-infected genotype 1 HCV, treatment-naïve subjects
Pharmacodynamic
- to evaluate the relationship between the metrics of the reduction from baseline in serum HCV RNA and PK parameters of INX-08189 and the metabolite INX-08032
Efficacy
- to measure the maximal reduction in plasma HCV RNA by ascending oral dose level of INX-08189 given once a day for seven (7) days in chronically-infected genotype 1 HCV, treatment-naïve subjects
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Arm 1: INX-08189 (9 mg) or Placebo | Experimental | Drug: INX-08189, Drug: Placebo matching with INX-08189 |
| Arm 2: INX-08189 (25 mg) or Placebo | Experimental | Drug: INX-08189, Drug: Placebo matching with INX-08189 |
| Arm 3: INX-08189 (50 mg + 9 mg) or Placebo | Experimental | Drug: INX-08189, Drug: Placebo matching with INX-08189 |
| Arm 4: INX-08189 (50 mg) or Placebo | Experimental | Drug: INX-08189, Drug: Placebo matching with INX-08189 |
| Arm 5: INX-08189 (9 mg) or Placebo + Ribavirin | Experimental | Drug: INX-08189, Drug: Placebo matching with INX-08189, Drug: Ribavirin |
| Arm 6: INX-08189 (25 mg) or Placebo + Ribavirin | Experimental | Drug: INX-08189, Drug: Placebo matching with INX-08189, Drug: Ribavirin |
| Arm 7: INX-08189 (100 mg) or Placebo | Experimental | Drug: INX-08189, Drug: Placebo matching with INX-08189 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Males \& females, 18 - 65 years of age inclusive(BMI of at least 18kg/m2 not exceeding 36kg/m2);
- Diagnosis of chronic HCV by 1 previous PCR result prior to screening, with a positive HCV viral load of at least 100,000IU/ml at screening measured by quantitative PCR;
- HCV genotype 1 per central lab testing report;
- HCV treatment-naïve (defined as no prior treatment with interferon, pegylated interferon, ribavirin, or any HCV direct acting anti-viral drugs);
- Liver biopsy consistent with chronic HCV infection but non-cirrhotic as judged by a pathologist (Knodell < 3, Metavir <2, Ishak <4, or Batts \& Ludwig <2) within the last 2 years \& before Visit 2 (biopsy can be done within screening period);
Key exclusion criteria (18 listed)
- Advanced liver disease, cirrhosis, or with signs of decompensated liver disease such as variceal bleeding, ascites, hepatic encephalopathy, active jaundice (total bilirubin > 2, or other evidence of decompensated liver disease;
- Co-infection with HBV or HIV (positive test for HBsAg or anti-HIV Ab);
- Acute cardiac ischemia, unstable heart disease or clinically symptomatic cardiac abnormalities apparent on ECG \& PE, or a QTcB interval at Visit 1 of ≥ to 450ms by Bazette's correction, or personal or family history of Torsades de pointes;
- Use of the following medications concurrently or within the 30 days prior to Screening associated with QT prolongation: macrolides, antiarrhythmic agents, azoles, fluoroquinolones, \& tricyclic anti-depressants (methadone use allowed);
- Use of immunosuppressive or immune-modulating agents (including corticosteroids \& immunosuppressive agents) or presence of an immunologically-mediated autoimmune disease (other than asthma) or history of organ transplantation (inhaled steroids for asthma \& topical steroid for minor skin conditions allowed);
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 |
|---|---|---|
| INX-08189Capsules, Oral, 9 mg, Once Daily, 7 Days | Drug | Arm 1: INX-08189 (9 mg) or Placebo |
| INX-08189Capsule, Oral, 25 mg, Once Daily, 7 days | Drug | Arm 2: INX-08189 (25 mg) or Placebo, Arm 6: INX-08189 (25 mg) or Placebo + Ribavirin |
| INX-08189Capsules, Oral, 50 mg, Single Dose, 1 day | Drug | Arm 3: INX-08189 (50 mg + 9 mg) or Placebo |
| INX-08189Capsules, Oral, 9 mg, Once daily, 6 days | Drug | Arm 3: INX-08189 (50 mg + 9 mg) or Placebo |
| INX-08189Capsules, Oral, 50 mg, Once daily, 7 days | Drug | Arm 4: INX-08189 (50 mg) or Placebo |
| INX-08189Capsules, Oral, 9 mg, Once daily, 7 days | Drug | Arm 5: INX-08189 (9 mg) or Placebo + Ribavirin |
| INX-08189Capsules, Oral, 100 mg, Once daily, 7 days | Drug | Arm 7: INX-08189 (100 mg) or Placebo |
| Placebo matching with INX-08189Capsules, Oral, 0 mg, Once daily, 7 days | Drug | Arm 1: INX-08189 (9 mg) or Placebo, Arm 2: INX-08189 (25 mg) or Placebo, Arm 3: INX-08189 (50 mg + 9 mg) or Placebo, Arm 4: INX-08189 (50 mg) or Placebo, Arm 5: INX-08189 (9 mg) or Placebo + Ribavirin, Arm 6: INX-08189 (25 mg) or Placebo + Ribavirin, Arm 7: INX-08189 (100 mg) or Placebo |
| RibavirinCapsules, Oral, 1000 or 1200 mg daily (delivered in weight-adjusted am/pm divided dose), 7 days | Drug | Arm 5: INX-08189 (9 mg) or Placebo + Ribavirin, Arm 6: INX-08189 (25 mg) or Placebo + Ribavirin |
Primary outcome
Safety will be evaluated in an integrated way on the basis of the Adverse Event profiles, changes in laboratory values (serum chemistry, hematology and urinalysis), ECG data, and vital signs, viral resistance testing and results of Physical Exams.
Time frame: periodically over 14 days
PK parameters following administration of INX-08189 will be determined using concentration data obtained via the assay of INX-08189 and INX-08032 in plasma, and the analysis of INX-08032 in urine
Time frame: periodically over 14 days
The primary efficacy outcome is the maximum change from baseline in HCV RNA following 7 days of dosing.
Time frame: 7 days
1 secondary outcome
Secondary efficacy outcome measures include the change in HCV RNA over time during the seven days of dosing and during the follow-up period thereafter. Additionally, viral load changes will be compared across the two genotypes 1a and 1b.
Time frame: 14 days
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 12 Jul 2012.
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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INX-08189 and Ribavirin in people with HCV (Genotype 1), run by Bristol-Myers Squibb at 4 sites in 2 countries.
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 11 inclusion and 18 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 12 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Safety will be evaluated in an integrated way on the basis of the Adverse Event profiles, changes in laboratory values (serum chemistry, hematology and urinalysis), ECG data, and vital signs, viral resistance testing and results of Physical Exams. (time frame: periodically over 14 days). 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 12 Jul 2012.