Trial Outcomes & Findings for Influence of Ribavirin on the Initial Virological Response in Treatment Naïve Patients With Hepatitis C Genotype 1 Infection (NCT NCT02716779)
NCT ID: NCT02716779
Last Updated: 2016-08-22
Results Overview
To investigate possible action mechanisms, three different models were fitted to viruskinetic data and evaluated using related log-likelihood function values. These models were designed assuming individual effects with respect to infectiousness (model 1), virus production (model 2) or degradation of infected cells rate (model 3). The following viruskinetic parameters were fitted in each model: initial viral load, loss rate of infected cells (delta), effectivity of interferon with respect to a pharmacokinetic-pharmacodynamic model. A lower log likelihood function value indicates a lesser fit for the model.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
68 participants
Primary outcome timeframe
Up to Day 126
Results posted on
2016-08-22
Participant Flow
Enrollment was 68: 1 participant withdrew during the screening phase and 67 participants were randomized.
Participant milestones
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40 kilodalton \[KD\]) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg orally (PO) (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Placebo
Participants with chronic hepatitis C, genotype 1, received ribavirin matching placebo for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40 kilodalton \[KD\]) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Placebo: Ribavirin matching placebo orally (PO) twice daily for 6 weeks.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40 kilodalton \[KD\]) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg orally (PO) (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
|---|---|---|---|
|
Monotherapy
STARTED
|
14
|
26
|
27
|
|
Monotherapy
COMPLETED
|
14
|
25
|
26
|
|
Monotherapy
NOT COMPLETED
|
0
|
1
|
1
|
|
Combination Therapy
STARTED
|
14
|
25
|
26
|
|
Combination Therapy
COMPLETED
|
14
|
23
|
25
|
|
Combination Therapy
NOT COMPLETED
|
0
|
2
|
1
|
Reasons for withdrawal
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40 kilodalton \[KD\]) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg orally (PO) (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Placebo
Participants with chronic hepatitis C, genotype 1, received ribavirin matching placebo for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40 kilodalton \[KD\]) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Placebo: Ribavirin matching placebo orally (PO) twice daily for 6 weeks.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40 kilodalton \[KD\]) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg orally (PO) (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
|---|---|---|---|
|
Monotherapy
Adverse Event
|
0
|
1
|
1
|
|
Combination Therapy
Adverse Event
|
0
|
2
|
1
|
Baseline Characteristics
Influence of Ribavirin on the Initial Virological Response in Treatment Naïve Patients With Hepatitis C Genotype 1 Infection
Baseline characteristics by cohort
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=14 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Placebo
n=26 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin matching placebo for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Placebo: Ribavirin matching placebo orally (PO) twice daily for 6 weeks.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=27 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total
n=67 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
45.8 years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
48.2 years
STANDARD_DEVIATION 15.4 • n=7 Participants
|
50.2 years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
48.5 years
STANDARD_DEVIATION 14.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to Day 126Population: Per Protocol (PP) population: participants with 6 weeks of monotherapy and at least 4 weeks combination therapy as well as three quantitative HCV-RNA measurements (baseline, period 1, period 2), no major protocol violations, no treatment interruption and no dose reduction below 80% of the planned medication within the first 10 therapy weeks.
To investigate possible action mechanisms, three different models were fitted to viruskinetic data and evaluated using related log-likelihood function values. These models were designed assuming individual effects with respect to infectiousness (model 1), virus production (model 2) or degradation of infected cells rate (model 3). The following viruskinetic parameters were fitted in each model: initial viral load, loss rate of infected cells (delta), effectivity of interferon with respect to a pharmacokinetic-pharmacodynamic model. A lower log likelihood function value indicates a lesser fit for the model.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=13 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=23 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=61 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Log Likelihood Median Values of Hepatitis C-Virus (HCV) Kinetic Models for Quantitative HCV Ribonucleic Acid (RNA) Measurement With Various Assumptions of Ribavirin Mechanism of Action
Model 1= infectiousness
|
-27.0 log likelihood function value
Interval -34.5 to -14.0
|
-21.4 log likelihood function value
Interval -24.7 to -15.2
|
-22.2 log likelihood function value
Interval -26.0 to -19.3
|
|
Log Likelihood Median Values of Hepatitis C-Virus (HCV) Kinetic Models for Quantitative HCV Ribonucleic Acid (RNA) Measurement With Various Assumptions of Ribavirin Mechanism of Action
Model 2= virus production
|
-28.2 log likelihood function value
Interval -35.0 to -14.3
|
-23.8 log likelihood function value
Interval -27.5 to -21.6
|
-23.9 log likelihood function value
Interval -27.4 to -21.6
|
|
Log Likelihood Median Values of Hepatitis C-Virus (HCV) Kinetic Models for Quantitative HCV Ribonucleic Acid (RNA) Measurement With Various Assumptions of Ribavirin Mechanism of Action
Model 3= degradation rate
|
-27.1 log likelihood function value
Interval -33.2 to -14.0
|
-20.7 log likelihood function value
Interval -25.5 to -16.0
|
-23.1 log likelihood function value
Interval -26.5 to -18.4
|
SECONDARY outcome
Timeframe: At screening (Days -56 to -1), at end of monotherapy (Week 6) and at end of combination therapy (Week 18)Population: Intent-to-treat (ITT) population includes all randomized participants who received at least one dose of study drug. Here, 'n' is the number of evaluable participants.
SF-36 is a psychometric scale to quantify health conditions. This psychometric scale has 8 dimensions of the subjective health status and consists of 36 individual items that have a varying number of related item scores (ranging from "yes/no" up to a 6-point scale). At first the raw scores were determined by summation over all items and weighted accordingly. Afterwards the raw scores were transformed to ranges of 0-100 with 100 being the highest level of health and compared to published reference scales. The following eight dimensions of subjective health conditions were considered: physical functioning index, role physical index, pain, general health perception, vitality, social functioning index, role emotional index and mental health index. The SF36 questionnaire had to be answered by the patients at screening before monotherapy, after monotherapy and at the end of the study (=end of combination therapy).
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=6 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=11 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=17 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Pain: End of combination therapy
|
72.3 units on a scale
Standard Deviation 32.2
|
56.0 units on a scale
Standard Deviation 11.8
|
60.1 units on a scale
Standard Deviation 34.8
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Social functioning index: End of monotherapy
|
72.9 units on a scale
Standard Deviation 22.9
|
68.2 units on a scale
Standard Deviation 24.0
|
80.1 units on a scale
Standard Deviation 22.6
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Mental health index: End of monotherapy
|
61.3 units on a scale
Standard Deviation 12.3
|
62.8 units on a scale
Standard Deviation 14.0
|
61.5 units on a scale
Standard Deviation 19.7
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Physical functioning index: Screening
|
95.6 units on a scale
Standard Deviation 5.2
|
76.5 units on a scale
Standard Deviation 20.2
|
79.7 units on a scale
Standard Deviation 28.7
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Physical functioning index: End of monotherapy
|
90.8 units on a scale
Standard Deviation 9.2
|
72.3 units on a scale
Standard Deviation 28.1
|
68.4 units on a scale
Standard Deviation 27.7
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Physical functioning index: End of comb. therapy
|
67.1 units on a scale
Standard Deviation 20.7
|
73.0 units on a scale
Standard Deviation 14.0
|
53.4 units on a scale
Standard Deviation 31.5
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Role physical index: Screening
|
75.0 units on a scale
Standard Deviation 41.8
|
55.6 units on a scale
Standard Deviation 41.0
|
62.5 units on a scale
Standard Deviation 40.8
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Role physical index: End of monotherapy
|
66.7 units on a scale
Standard Deviation 34.2
|
56.8 units on a scale
Standard Deviation 43.4
|
50.5 units on a scale
Standard Deviation 40.5
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Role physical index: End of combination therapy
|
25.0 units on a scale
Standard Deviation 38.7
|
40.0 units on a scale
Standard Deviation 35.7
|
29.7 units on a scale
Standard Deviation 40.0
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Pain: Screening
|
89.3 units on a scale
Standard Deviation 17.0
|
70.3 units on a scale
Standard Deviation 26.8
|
70.0 units on a scale
Standard Deviation 30.8
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Pain: End of monotherapy
|
73.2 units on a scale
Standard Deviation 23.3
|
61.5 units on a scale
Standard Deviation 27.4
|
66.0 units on a scale
Standard Deviation 29.6
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
General health perception: Screening
|
58.6 units on a scale
Standard Deviation 12.9
|
53.6 units on a scale
Standard Deviation 14.5
|
62.9 units on a scale
Standard Deviation 14.5
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
General health perception: End of monotherapy
|
58.2 units on a scale
Standard Deviation 7.6
|
59.2 units on a scale
Standard Deviation 16.9
|
54.3 units on a scale
Standard Deviation 18.0
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
General health perception: End of comb. therapy
|
60.0 units on a scale
Standard Deviation 14.3
|
55.2 units on a scale
Standard Deviation 15.0
|
47.1 units on a scale
Standard Deviation 20.6
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Vitality: Screening
|
54.2 units on a scale
Standard Deviation 9.2
|
52.8 units on a scale
Standard Deviation 21.5
|
50.9 units on a scale
Standard Deviation 18.9
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Vitality: End of monotherapy
|
45.0 units on a scale
Standard Deviation 15.2
|
44.1 units on a scale
Standard Deviation 16.3
|
41.8 units on a scale
Standard Deviation 20.1
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Vitality: End of combination therapy
|
40.8 units on a scale
Standard Deviation 14.6
|
32.5 units on a scale
Standard Deviation 12.1
|
39.8 units on a scale
Standard Deviation 16.1
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Social functioning index: Screening
|
75.0 units on a scale
Standard Deviation 23.7
|
79.2 units on a scale
Standard Deviation 24.2
|
83.8 units on a scale
Standard Deviation 20.6
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Social functioning index: End of comb. therapy
|
68.8 units on a scale
Standard Deviation 23.4
|
61.3 units on a scale
Standard Deviation 19.9
|
56.3 units on a scale
Standard Deviation 25.8
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Role emotional index: Screening
|
55.6 units on a scale
Standard Deviation 50.2
|
66.7 units on a scale
Standard Deviation 50.0
|
62.5 units on a scale
Standard Deviation 43.7
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Role emotional index: End of monotherapy
|
55.6 units on a scale
Standard Deviation 50.2
|
69.7 units on a scale
Standard Deviation 45.8
|
53.3 units on a scale
Standard Deviation 51.6
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Role emotional index: End of combination therapy
|
33.3 units on a scale
Standard Deviation 51.6
|
50.0 units on a scale
Standard Deviation 42.3
|
35.4 units on a scale
Standard Deviation 39.4
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Mental health index: Screening
|
68.5 units on a scale
Standard Deviation 9.1
|
63.1 units on a scale
Standard Deviation 18.1
|
64.5 units on a scale
Standard Deviation 15.4
|
|
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
Mental health index: End of combination therapy
|
72.2 units on a scale
Standard Deviation 9.0
|
61.6 units on a scale
Standard Deviation 13.2
|
47.7 units on a scale
Standard Deviation 23.0
|
SECONDARY outcome
Timeframe: Up to Day 126Population: All evaluable participants of the Intent-to-Treat (ITT) population, who were documented for a total of 126 days of the treatment period.
HCV-RNA level was measured at each visit by a central laboratory. Treatment response was estimated applying the following definitions of response/non-response: 1) Adequate first phase decline: HCV RNA decline ≥ 0.5 log10 International Units/milliliter (IU/mL) from time 0 to 48 hours of PEG-IFN treatment (PEG-IFN arm: day 0 - day 2; placebo and ribavirin arm: day 42-day 44), 2) Rapid virologic response: HCV RNA \< 15 IU/mL (=detection limit) on day 70, 3) Complete early virologic response: HCV RNA \< 15 IU/mL on day 126, 4) Partial early virologic response (log decrease): HCV RNA decrease ≥ 2 log10 IU/mL from day 0 to day 126, 5) Partial early virologic response (cut off): HCV RNA \<30000 IU/mL on day 126, 6) Non-response: HCV RNA decrease \<2 log10 IU/mL from day 0 to day 126, 7) Null-response: HCV RNA decrease \<1 log10 IU/mL from day 0 to day 28 and from day 0 to day 70 for PEG-IFN arm and placebo / ribavirin arm, respectively.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=14 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=23 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Percentage of Participants With Treatment Response
Adequate first phase decline
|
79 percentage of participants
|
65 percentage of participants
|
72 percentage of participants
|
|
Percentage of Participants With Treatment Response
Rapid virologic response
|
43 percentage of participants
|
30 percentage of participants
|
20 percentage of participants
|
|
Percentage of Participants With Treatment Response
Complete early virologic response
|
64 percentage of participants
|
48 percentage of participants
|
72 percentage of participants
|
|
Percentage of Participants With Treatment Response
Partial early virologic response (log decrease)
|
79 percentage of participants
|
78 percentage of participants
|
84 percentage of participants
|
|
Percentage of Participants With Treatment Response
Partial early virologic response (cut off)
|
79 percentage of participants
|
78 percentage of participants
|
84 percentage of participants
|
|
Percentage of Participants With Treatment Response
Non-response
|
21 percentage of participants
|
22 percentage of participants
|
16 percentage of participants
|
|
Percentage of Participants With Treatment Response
Null responder
|
36 percentage of participants
|
26 percentage of participants
|
12 percentage of participants
|
SECONDARY outcome
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.Population: All evaluable participants of the ITT population, who were documented for a total of 126 days of the treatment period.
Evaluation of ribavirin arm after Day 0. Evaluation of placebo and PEG-IFN arms after Day 42.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=13 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=23 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve (AUC) of Ribavirin
|
186.6 (microgram/milliliter)*day ([mcg/ml]*d)
Interval 142.3 to 201.4
|
179.4 (microgram/milliliter)*day ([mcg/ml]*d)
Interval 142.6 to 203.8
|
290.1 (microgram/milliliter)*day ([mcg/ml]*d)
Interval 257.6 to 370.5
|
SECONDARY outcome
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.Population: All evaluable participants of the ITT population, who were documented for a total of 126 days of the treatment period.
Cmax was obtained directly from the concentration-time data. Evaluation of ribavirin arm after day 0. Evaluation of placebo and PEG-IFN arms after day 42.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=13 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=23 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Maximum Concentration (Cmax) of Ribavirin
|
2.95 mcg/ml
Interval 2.79 to 3.6
|
2.83 mcg/ml
Interval 2.34 to 3.26
|
3.37 mcg/ml
Interval 2.93 to 4.19
|
SECONDARY outcome
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.Population: All evaluable participants of the ITT population, who were documented for a total of 126 days of the treatment period.
Tmax was obtained directly from the concentration-time data. Evaluation of ribavirin arm after day 0. Evaluation of placebo and PEG-IFN arms after day 42.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=13 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=23 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of Ribavirin
|
6.0 weeks
Interval 4.0 to 12.0
|
8.0 weeks
Interval 6.0 to 12.0
|
6.4 weeks
Interval 6.1 to 8.0
|
SECONDARY outcome
Timeframe: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126Population: All evaluable participants of the ITT population, who were documented for a total of 126 days of the treatment period.
Evaluation of PEG-IFN arm after Day 0. Evaluation of ribavirin and placebo arms after Day 42.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=14 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=22 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve (AUC) of PEG-IFN
|
2097.9 (nanogram/milliliter)*day ([ng/ml]*d)
Interval 1763.5 to 2997.3
|
1270.4 (nanogram/milliliter)*day ([ng/ml]*d)
Interval 931.8 to 1572.0
|
1164.9 (nanogram/milliliter)*day ([ng/ml]*d)
Interval 925.2 to 1461.3
|
SECONDARY outcome
Timeframe: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126Population: All evaluable participants of the ITT population, who were documented for a total of 126 days of the treatment period.
Cmax was obtained directly from the concentration-time data. Evaluation of PEG-IFN arm after day 0. Evaluation of ribavirin and placebo arms after day 42.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=14 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=22 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Maximum Concentration (Cmax) of PEG-IFN
|
28.77 ng/ml
Interval 22.8 to 32.38
|
20.36 ng/ml
Interval 16.92 to 25.83
|
19.8 ng/ml
Interval 15.8 to 22.3
|
SECONDARY outcome
Timeframe: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126Population: All evaluable participants of the ITT population, who were documented for a total of 126 days of the treatment period.
Tmax was obtained directly from the concentration-time data. Evaluation of PEG-IFN arm after day 0. Evaluation of ribavirin and placebo arms after day 42.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=14 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=22 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of PEG-IFN
|
6.3 weeks
Interval 6.1 to 8.0
|
12.0 weeks
Interval 6.0 to 12.0
|
6.0 weeks
Interval 6.0 to 12.0
|
SECONDARY outcome
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.Population: All evaluable participants of the ITT population, who were documented for a total of 126 days of the treatment period.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=14 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=23 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve (AUC) of Glutamate-Pyruvate Transaminase (GPT)
|
5078.3 (Units/liter)*day ([U/L]*d)
Interval 4358.3 to 6576.5
|
7233.5 (Units/liter)*day ([U/L]*d)
Interval 5337.3 to 8656.3
|
5231.3 (Units/liter)*day ([U/L]*d)
Interval 3917.0 to 5852.5
|
SECONDARY outcome
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.Population: All evaluable participants of the ITT population, who were documented for a total of 126 days of the treatment period.
Cmax was obtained directly from the concentration-time data.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=14 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=23 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Maximum Concentration (Cmax) of GPT
|
68.5 U/L
Interval 59.0 to 112.0
|
88.0 U/L
Interval 67.0 to 123.0
|
75.0 U/L
Interval 56.0 to 110.0
|
SECONDARY outcome
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.Population: All evaluable participants of the ITT population, who were documented for a total of 126 days of the treatment period.
Tmax was obtained directly from the concentration-time data.
Outcome measures
| Measure |
Pegylated Interferon (PEG-IFN) Alfa-2a
n=14 Participants
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Ribavirin
n=23 Participants
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.
|
Total Participant Group
n=25 Participants
Combined group of PEG IFN alfa-2a, matching placebo and ribavirin arms.
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of GPT
|
2.8 days
Interval 2.0 to 28.0
|
14.0 days
Interval 10.0 to 42.5
|
3.0 days
Interval 2.0 to 7.0
|
Adverse Events
PEG-IFN Alfa-2a, Period 1 Monotherapy
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Placebo, Period 1 Monotherapy
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Ribavirin, Period 1 Monotherapy
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
PEG-IFN Alfa-2a, Period 2 Combination Therapy
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Placebo, Period 2 Combination Therapy
Serious events: 2 serious events
Other events: 23 other events
Deaths: 0 deaths
Ribavirin, Period 2 Combination Therapy
Serious events: 2 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PEG-IFN Alfa-2a, Period 1 Monotherapy
n=14 participants at risk
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks in period 1.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks.
|
Placebo, Period 1 Monotherapy
n=26 participants at risk
Participants with chronic hepatitis C, genotype 1, received placebo PO for 6 weeks in period 1.
Placebo: Ribavirin matching placebo orally (PO) twice daily for 6 weeks.
|
Ribavirin, Period 1 Monotherapy
n=27 participants at risk
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks in period 1.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks.
|
PEG-IFN Alfa-2a, Period 2 Combination Therapy
n=14 participants at risk
In period 2 participants, who received PEG-IFN monotherapy in period 1, received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks.
|
Placebo, Period 2 Combination Therapy
n=25 participants at risk
In period 2 participants, who received placebo in period 1, received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks.
|
Ribavirin, Period 2 Combination Therapy
n=26 participants at risk
In period 2 participants, who received ribavirin monotherapy in period 1, received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks.
|
|---|---|---|---|---|---|---|
|
Psychiatric disorders
Depression
|
0.00%
0/14 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
4.0%
1/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Eye disorders
Retinal haemorrhage
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
4.0%
1/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Infections and infestations
Otitis media
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
|
Surgical and medical procedures
Psychotherapy
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
Other adverse events
| Measure |
PEG-IFN Alfa-2a, Period 1 Monotherapy
n=14 participants at risk
Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks in period 1.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks.
|
Placebo, Period 1 Monotherapy
n=26 participants at risk
Participants with chronic hepatitis C, genotype 1, received placebo PO for 6 weeks in period 1.
Placebo: Ribavirin matching placebo orally (PO) twice daily for 6 weeks.
|
Ribavirin, Period 1 Monotherapy
n=27 participants at risk
Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks in period 1.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks.
|
PEG-IFN Alfa-2a, Period 2 Combination Therapy
n=14 participants at risk
In period 2 participants, who received PEG-IFN monotherapy in period 1, received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks.
|
Placebo, Period 2 Combination Therapy
n=25 participants at risk
In period 2 participants, who received placebo in period 1, received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks.
|
Ribavirin, Period 2 Combination Therapy
n=26 participants at risk
In period 2 participants, who received ribavirin monotherapy in period 1, received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.
Pegylated Interferon (PEG-IFN) alfa-2a: Pegylated Interferon (PEG-IFN) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks.
Ribavirin: Ribavirin, 1000 mg PO (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks.
|
|---|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
3.7%
1/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
4.0%
1/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
8.0%
2/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
7.7%
2/26 • Up to Day 126
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Eye disorders
Keratoconjunctivitis sicca
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Eye disorders
Vision blurred
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Gastrointestinal disorders
Nausea
|
14.3%
2/14 • Up to Day 126
|
7.7%
2/26 • Up to Day 126
|
3.7%
1/27 • Up to Day 126
|
28.6%
4/14 • Up to Day 126
|
32.0%
8/25 • Up to Day 126
|
19.2%
5/26 • Up to Day 126
|
|
Gastrointestinal disorders
Diarrhoea
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
3.7%
1/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
20.0%
5/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
|
Gastrointestinal disorders
Abdominal pain lower
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
4.0%
1/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
|
Gastrointestinal disorders
Toothache
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
4.0%
1/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
8.0%
2/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
General disorders
Fatigue
|
21.4%
3/14 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
14.8%
4/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
36.0%
9/25 • Up to Day 126
|
23.1%
6/26 • Up to Day 126
|
|
General disorders
Chills
|
14.3%
2/14 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
12.0%
3/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
|
General disorders
Influenza like illness
|
21.4%
3/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
20.0%
5/25 • Up to Day 126
|
34.6%
9/26 • Up to Day 126
|
|
General disorders
Asthenia
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
7.4%
2/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
General disorders
Pyrexia
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
12.0%
3/25 • Up to Day 126
|
11.5%
3/26 • Up to Day 126
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/14 • Up to Day 126
|
7.7%
2/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Infections and infestations
Cystitis
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Infections and infestations
Ear infection
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
3.7%
1/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
16.0%
4/25 • Up to Day 126
|
11.5%
3/26 • Up to Day 126
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/14 • Up to Day 126
|
7.7%
2/26 • Up to Day 126
|
3.7%
1/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.3%
2/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
3.7%
1/27 • Up to Day 126
|
14.3%
2/14 • Up to Day 126
|
8.0%
2/25 • Up to Day 126
|
15.4%
4/26 • Up to Day 126
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
20.0%
5/25 • Up to Day 126
|
7.7%
2/26 • Up to Day 126
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
12.0%
3/25 • Up to Day 126
|
7.7%
2/26 • Up to Day 126
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
8.0%
2/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
|
Nervous system disorders
Headache
|
14.3%
2/14 • Up to Day 126
|
15.4%
4/26 • Up to Day 126
|
14.8%
4/27 • Up to Day 126
|
14.3%
2/14 • Up to Day 126
|
40.0%
10/25 • Up to Day 126
|
19.2%
5/26 • Up to Day 126
|
|
Nervous system disorders
Dizziness
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
8.0%
2/25 • Up to Day 126
|
19.2%
5/26 • Up to Day 126
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
4.0%
1/25 • Up to Day 126
|
7.7%
2/26 • Up to Day 126
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/14 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
7.4%
2/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
16.0%
4/25 • Up to Day 126
|
7.7%
2/26 • Up to Day 126
|
|
Psychiatric disorders
Mood swings
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
8.0%
2/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
|
Psychiatric disorders
Depression
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
8.0%
2/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Psychiatric disorders
Initial insomnia
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
4.0%
1/25 • Up to Day 126
|
15.4%
4/26 • Up to Day 126
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
8.0%
2/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
20.0%
5/25 • Up to Day 126
|
15.4%
4/26 • Up to Day 126
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
14.3%
2/14 • Up to Day 126
|
8.0%
2/25 • Up to Day 126
|
15.4%
4/26 • Up to Day 126
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
|
Vascular disorders
Hypertension
|
0.00%
0/14 • Up to Day 126
|
0.00%
0/26 • Up to Day 126
|
0.00%
0/27 • Up to Day 126
|
7.1%
1/14 • Up to Day 126
|
0.00%
0/25 • Up to Day 126
|
3.8%
1/26 • Up to Day 126
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER