A Study to Assess the Anti-viral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 in Participants Infected With Hepatitis C-Virus (HCV)
Sponsor
Tibotec Pharmaceuticals, Ireland (Industry)
Overall Status
Completed
CT.gov ID
NCT00812331
Collaborator
(none)
37
11
5
8
3.4
0.4
Study Details
Study Description
Brief Summary
The purpose of this study is to assess anti-viral activity (inhibition of viral growth) of TMC435350 in genotype 2,3,4,5 and 6 hepatitis C virus infected participants who have never received treatment for their hepatitis C infection.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This is an open-label (all people know the identity of the intervention) study to assess the antiviral activity, safety, tolerability and pharmacokinetics (explores what the body does to the medication) of TMC435350 hereafter referred to as TMC435. Approximately 40 participants will be divided in 5 groups as per the genotype (8 participants each group). The study will include a screening phase (up to 6 weeks), treatment phase (7 days) and a follow-up phase (30-35 days after the last dose of study medication). Safety evaluations will include assessment of adverse events, clinical laboratory tests and cardiovascular safety.
Study Design
Study Type:
Interventional
Actual Enrollment
:
37 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Trial in Genotype 2, 3, 4, 5 and 6 Hepatitis C-infected Subjects to Evaluate the Antiviral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 Following 7 Days Once Daily Dosing as Monotherapy.
Study Start Date
:
Mar 1, 2009
Actual Primary Completion Date
:
Nov 1, 2009
Actual Study Completion Date
:
Nov 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Genotype 2 Participants with chronic genotype 2 hepatitis C virus (HCV) infection |
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
|
| Experimental: Genotype 3 Participants with chronic genotype 3 HCV infection |
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
|
| Experimental: Genotype 4 Participants with chronic genotype 4 HCV infection |
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
|
| Experimental: Genotype 5 Participants with chronic genotype 5 HCV infection |
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
|
| Experimental: Genotype 6 Participants with chronic genotype 6 HCV infection |
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels [Baseline, Day 3, and Day 7]
The table below shows the mean changes from baseline in HCV RNA values (log10 IU/mL) per genotype on Day 3 and Day 7 during the TMC435 treatment period.
Secondary Outcome Measures
- Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period [Baseline, Day 3, Day 5 and Day 7]
The table below shows the number of participants with a decrease from baseline of greater than or equal to 2 log10 IU/mL in HCV RNA during the 7-day TMC435 treatment period.
- Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period [Baseline, Day 3, Day 5 and Day 7]
The table below shows the number of participants with plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels below limit of quantification (less than 25 IU/mL) and limit of detection (less than 25 IU/mL undetectable), respectively, during the 7-day TMC435 treatment period.
- Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period [During the 7-day of TMC435 treatment period]
The table below shows the number of participants who experienced viral breakthrough (defined as an increase greater than 1 log10 IU/mL in plasma level of hepatitis C virus [HCV] ribonucleic acid [RNA] from the lowest level reached, or a HCV RNA level greater than 100 IU/mL in participants who previously had HCV RNA levels undetectable [less than 25 IU/mL undetectable] or not quantifiable [less than 25 IU/mL detectable]) during the 7-day TMC435 treatment period.
- Predose Plasma Concentration (C0h) of TMC435 [Predose on Day 7]
The table below shows the median predose plasma concentration (C0h) for all participants on Day 7 of the TMC435 treatment period.
- Minimum Plasma Concentration (Cmin) of TMC435 [Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7]
The table below shows the median minimum plasma concentration (Cmin) for all participants on Day 7 of the TMC435 treatment period.
- Maximum Plasma Concentration (Cmax) of TMC435 [Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7]
The table below shows the median maximum plasma concentration (Cmax) for all participants by genotype of hepatitis C virus infection on Day 7 of the TMC435 treatment period.
- Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 [Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7]
The table below shows the median time in hours for all participants (by genotype of hepatitis C virus infection) to reach the maximum plasma concentration (tmax) of TMC435 following treatment.
- Average Steady-State Plasma Concentration (Css,av) of TMC435 [Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7]
The table below shows the average steady-state TMC435 plasma concentration (Css,av) for all participants by genotype of hepatitis C virus infection on Day 7 during the TMC435 treatment period.
- Fluctuation Index (FI) of TMC435 [Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7]
The table below shows the percentage of fluctuation (FI) (defined as the variation between maximum and minimum TMC435 plasma concentrations at steady-state) of TMC435 on Day 7 for participants by genotype of hepatitis C virus infection.
- Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435 [Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7]
The table below shows the area under the plasma concentration-time curve from the time of administration up to 24 hours after dosing (AUC24h) of TMC435 on Day 7 for all participants by genotype of hepatitis C virus infection.
- Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435 [Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7]
The table below shows the area under the plasma concentration-time curve from time of administration up to the last time point with a measurable concentration after dosing (AUClast) on Day 7 for TMC435 by genotype of hepatitis C virus infection.
- Elimination Rate Constant of TMC435 [Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7]
In the table below, median values for the elimination rate constant (the rate at which a drug is removed from the body expressed per unit of time, e.g., fraction/hour) for TMC435 are shown for participants by genotype of hepatitis C virus infection.
- Terminal Elimination Half-life (t1/2,Term) of TMC435 [Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7]
The table below shows the terminal plasma half-life for TMC435 in participants analyzed by genotype of hepatitis C virus infection. The terminal plasma half-life of a drug is the time in hours required for the concentration of a drug in the body to fall to 50% after having reached a state of equilibrium following administration.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Participants with documented chronic genotype 2, 3, 4, 5 or 6 hepatitis C virus (HCV) infection
-
Participants who have never received treatment for their HCV infection
-
Participants with either no cirrhosis or up to Child Pugh A liver disease
-
Participants with plasma HCV genotype level of more than or equal to 100, 000 IU/mL at screening
Exclusion Criteria:
-
Evidence of Child Pugh B or C liver disease at screening, decompensated liver disease defined as prior or current history of ascities, hepatic encephalopathy, esophageal or gastric varices
-
Participants with diagnosed or suspected hepatocellular carcinoma
-
Participants coinfected with human immunodeficiency virus type 1 or 2, or hepatitis A or B virus infection or active tuberculosis at screening
-
Participants with any active clinically significant disease, or medical history or physical examination or electrocardiogram findings during screening
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Brugge | Belgium | |||
| 2 | Brussels | Belgium | |||
| 3 | Bruxelles | Belgium | |||
| 4 | Gent | Belgium | |||
| 5 | Leuven | Belgium | |||
| 6 | Berlin | Germany | |||
| 7 | Frankfurt N/A | Germany | |||
| 8 | Freiburg | Germany | |||
| 9 | Hannover | Germany | |||
| 10 | Bangkok | Thailand | |||
| 11 | Chiang Mai | Thailand |
Sponsors and Collaborators
- Tibotec Pharmaceuticals, Ireland
Investigators
- Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial, Tibotec Pharmaceuticals, Ireland
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00812331
Other Study ID Numbers:
- CR012604
- TMC435350-TiDP16-C202
First Posted:
Dec 22, 2008
Last Update Posted:
Jul 28, 2014
Last Verified:
Jul 1, 2014
Keywords provided by Tibotec Pharmaceuticals, Ireland
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 37 participants from 3 countries were enrolled and started treatment in the study (17 participants in Belgium, 12 participants in Germany, and 8 participants in Thailand). |
|---|---|
| Pre-assignment Detail | A total of 48 participants were screened of which 11 participants were not treated with TMC435. A total of 37 participants received study medication. |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | Participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | Participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days |
| Period Title: Overall Study | |||||
| STARTED | 6 | 8 | 8 | 7 | 8 |
| COMPLETED | 5 | 8 | 8 | 7 | 8 |
| NOT COMPLETED | 1 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | Participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | Participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | Total of all reporting groups |
| Overall Participants | 6 | 8 | 8 | 7 | 8 | 37 |
| Age (years) [Median (Full Range) ] | ||||||
| Median (Full Range) [years] |
43
|
42
|
47
|
65
|
49
|
48
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
4
66.7%
|
3
37.5%
|
5
62.5%
|
4
57.1%
|
2
25%
|
18
48.6%
|
| Male |
2
33.3%
|
5
62.5%
|
3
37.5%
|
3
42.9%
|
6
75%
|
19
51.4%
|
| Race/Ethnicity, Customized (Number) [Number] | ||||||
| White |
5
83.3%
|
7
87.5%
|
6
75%
|
7
100%
|
0
0%
|
25
67.6%
|
| Asian |
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
8
100%
|
9
24.3%
|
| Black |
1
16.7%
|
0
0%
|
2
25%
|
0
0%
|
0
0%
|
3
8.1%
|
Outcome Measures
| Title | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels |
|---|---|
| Description | The table below shows the mean changes from baseline in HCV RNA values (log10 IU/mL) per genotype on Day 3 and Day 7 during the TMC435 treatment period. |
| Time Frame | Baseline, Day 3, and Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Day 3 |
-2.02
(0.625)
|
0.16
(0.263)
|
-3.43
(0.167)
|
-2.71
(0.335)
|
-3.57
(0.197)
|
| Day 7 |
-2.46
(0.538)
|
-0.13
(0.175)
|
-3.66
(0.320)
|
-2.43
(0.357)
|
-4.40
(0.222)
|
| Title | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period |
|---|---|
| Description | The table below shows the number of participants with a decrease from baseline of greater than or equal to 2 log10 IU/mL in HCV RNA during the 7-day TMC435 treatment period. |
| Time Frame | Baseline, Day 3, Day 5 and Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) Population- all randomized subjects who received at least 1 dose of study medication (TMC435) |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Day 3 |
3
50%
|
0
0%
|
8
100%
|
6
85.7%
|
8
100%
|
| Day 5 |
3
50%
|
0
0%
|
8
100%
|
5
71.4%
|
8
100%
|
| Day 7 |
3
50%
|
0
0%
|
8
100%
|
5
71.4%
|
8
100%
|
| Title | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period |
|---|---|
| Description | The table below shows the number of participants with plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels below limit of quantification (less than 25 IU/mL) and limit of detection (less than 25 IU/mL undetectable), respectively, during the 7-day TMC435 treatment period. |
| Time Frame | Baseline, Day 3, Day 5 and Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) Population - all randomized subjects who received at least 1 dose of study medication (TMC435) |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Day 3 (less than 25 IU/mL) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Day 3 (less than 25 IU/mL undetectable) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Day 5 (less than 25 IU/mL) |
0
0%
|
0
0%
|
2
25%
|
0
0%
|
1
12.5%
|
| Day 5 (less than 25 IU/mL undetectable) |
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
| Day 7 (less than 25 IU/mL) |
0
0%
|
0
0%
|
3
37.5%
|
0
0%
|
1
12.5%
|
| Day 7 (less than 25 IU/mL undetectable) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period |
|---|---|
| Description | The table below shows the number of participants who experienced viral breakthrough (defined as an increase greater than 1 log10 IU/mL in plasma level of hepatitis C virus [HCV] ribonucleic acid [RNA] from the lowest level reached, or a HCV RNA level greater than 100 IU/mL in participants who previously had HCV RNA levels undetectable [less than 25 IU/mL undetectable] or not quantifiable [less than 25 IU/mL detectable]) during the 7-day TMC435 treatment period. |
| Time Frame | During the 7-day of TMC435 treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Number [Participants] |
0
0%
|
1
12.5%
|
2
25%
|
3
42.9%
|
0
0%
|
| Title | Predose Plasma Concentration (C0h) of TMC435 |
|---|---|
| Description | The table below shows the median predose plasma concentration (C0h) for all participants on Day 7 of the TMC435 treatment period. |
| Time Frame | Predose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [ng/mL] |
3720
|
1310
|
6270
|
4650
|
5440
|
| Title | Minimum Plasma Concentration (Cmin) of TMC435 |
|---|---|
| Description | The table below shows the median minimum plasma concentration (Cmin) for all participants on Day 7 of the TMC435 treatment period. |
| Time Frame | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [ng/mL] |
3320
|
1110
|
5450
|
4230
|
4960
|
| Title | Maximum Plasma Concentration (Cmax) of TMC435 |
|---|---|
| Description | The table below shows the median maximum plasma concentration (Cmax) for all participants by genotype of hepatitis C virus infection on Day 7 of the TMC435 treatment period. |
| Time Frame | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [ng/mL] |
11250
|
6580
|
13500
|
13600
|
14800
|
| Title | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 |
|---|---|
| Description | The table below shows the median time in hours for all participants (by genotype of hepatitis C virus infection) to reach the maximum plasma concentration (tmax) of TMC435 following treatment. |
| Time Frame | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [hours] |
4.01
|
6.025
|
6.04
|
6.00
|
6.00
|
| Title | Average Steady-State Plasma Concentration (Css,av) of TMC435 |
|---|---|
| Description | The table below shows the average steady-state TMC435 plasma concentration (Css,av) for all participants by genotype of hepatitis C virus infection on Day 7 during the TMC435 treatment period. |
| Time Frame | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [ng/mL] |
7115
|
3081
|
8843
|
7850
|
9354
|
| Title | Fluctuation Index (FI) of TMC435 |
|---|---|
| Description | The table below shows the percentage of fluctuation (FI) (defined as the variation between maximum and minimum TMC435 plasma concentrations at steady-state) of TMC435 on Day 7 for participants by genotype of hepatitis C virus infection. |
| Time Frame | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [% fluctuation] |
130.2
|
149.4
|
95.38
|
93.12
|
88.16
|
| Title | Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435 |
|---|---|
| Description | The table below shows the area under the plasma concentration-time curve from the time of administration up to 24 hours after dosing (AUC24h) of TMC435 on Day 7 for all participants by genotype of hepatitis C virus infection. |
| Time Frame | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - as all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [ng*h/mL] |
170100
|
74670
|
212000
|
189000
|
227100
|
| Title | Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435 |
|---|---|
| Description | The table below shows the area under the plasma concentration-time curve from time of administration up to the last time point with a measurable concentration after dosing (AUClast) on Day 7 for TMC435 by genotype of hepatitis C virus infection. |
| Time Frame | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [ng*h/mL] |
268000
|
111500
|
365500
|
360000
|
411100
|
| Title | Elimination Rate Constant of TMC435 |
|---|---|
| Description | In the table below, median values for the elimination rate constant (the rate at which a drug is removed from the body expressed per unit of time, e.g., fraction/hour) for TMC435 are shown for participants by genotype of hepatitis C virus infection. |
| Time Frame | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [1/hour] |
0.05042
|
0.06024
|
0.04308
|
0.03826
|
0.03784
|
| Title | Terminal Elimination Half-life (t1/2,Term) of TMC435 |
|---|---|
| Description | The table below shows the terminal plasma half-life for TMC435 in participants analyzed by genotype of hepatitis C virus infection. The terminal plasma half-life of a drug is the time in hours required for the concentration of a drug in the body to fall to 50% after having reached a state of equilibrium following administration. |
| Time Frame | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435). |
| Arm/Group Title | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. | participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days. |
| Measure Participants | 6 | 8 | 8 | 7 | 8 |
| Median (Full Range) [hours] |
13.75
|
11.51
|
16.09
|
18.12
|
18.32
|
Adverse Events
| Time Frame | From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake. | |
|---|---|---|
| Adverse Event Reporting Description | 5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small. | |
| Arm/Group Title | Total | |
| Arm/Group Description | Participants with chronic genotype 2,3,4,5 or 6 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | |
All Cause Mortality |
||
| Total | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Total | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/37 (2.7%) | |
| Gastrointestinal disorders | ||
| Ileitis | 1/37 (2.7%) | |
Other (Not Including Serious) Adverse Events |
||
| Total | ||
| Affected / at Risk (%) | # Events | |
| Total | 22/37 (59.5%) | |
| Cardiac disorders | ||
| Palpitations | 2/37 (5.4%) | |
| Gastrointestinal disorders | ||
| Diarrhoea | 4/37 (10.8%) | |
| Constipation | 2/37 (5.4%) | |
| Lip swelling | 2/37 (5.4%) | |
| General disorders | ||
| Influenza like illness | 9/37 (24.3%) | |
| Fatigue | 4/37 (10.8%) | |
| Pyrexia | 2/37 (5.4%) | |
| Metabolism and nutrition disorders | ||
| Anorexia | 3/37 (8.1%) | |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 3/37 (8.1%) | |
| Myalgia | 3/37 (8.1%) | |
| Nervous system disorders | ||
| Headache | 5/37 (13.5%) | |
| Skin and subcutaneous tissue disorders | ||
| Pruritus | 4/37 (10.8%) | |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Global Clinical DVLP Manager |
|---|---|
| Organization | Janssen Research & Development United States |
| Phone | |
| ClinicalTrialDisclosure@its.jnj.com |
Responsible Party:
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00812331
Other Study ID Numbers:
- CR012604
- TMC435350-TiDP16-C202
First Posted:
Dec 22, 2008
Last Update Posted:
Jul 28, 2014
Last Verified:
Jul 1, 2014