| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01648140 | Dose Ranging of GSK2336805 in Combination Therapy | PHASE2 | COMPLETED | 286 | — | — | Aug 1, 2012 | Jul 16, 2014 | Jun 2, 2017 | 34 | United States, Belgium +4 |
| NCT01439373 | Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 With Peginterferon and Ribavirin in Chronic Hepatitis C Subjects | PHASE2 | COMPLETED | 16 | — | — | Jul 7, 2011 | Dec 5, 2011 | Dec 11, 2017 | 10 | United States, Puerto Rico |
eRVR is defined as plasma HCV ribonucleic acid (RNA) \<lower limit of quantification (LLOQ) and target not detected at Weeks 4 and 12. Participants who discontinued prior to Week 12 assessments or had missing HCV RNA values at Weeks 4 and 12 were treated as non-responders.
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding), symptom, or disease(new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect, important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.
Blood pressure measurements were taken to observe vital signs and included SBP and DBP at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and Post-treatment (PT) Follow Up (FU) Weeks 4, 12 and 24. Change from Baseline in SBP and DBP is summarized for each post-Baseline assessment up to Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Vital sign monitoring included heart rate, measured at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4, 12 and 24. Change from Baseline in heart rate is summarized for each post-Baseline assessment upto Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the basophils, eosinophils, lymphocytes, total neutrophils, platelet count and white blood cell count values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of red blood cell count at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the red blood cell count values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of hemoglobin at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hemoglobin values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of hematocrit at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hematocrit values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of mean corpuscle volume at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the mean corpuscle volume values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of albumin at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the albumin values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of ALP, ALT, AST, CK and GGT at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4 Change from Baseline in the ALP, ALT, AST, CK and GGT values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of direct bilirubin, total bilirubin and creatinine at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the direct bilirubin, total bilirubin and creatinine values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of Chloride, bicarbonate, glucose, potassium, sodium, inorganic phosphorus and urea/BUN at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the chloride, bicarbonate, glucose, potassium, sodium, inorganic phosphorus and urea/BUN values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Blood samples were collected for the measurement of Creatinine Clearance at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. It is estimated by Cockcroft-Gault Equation. Change from Baseline in the Creatinine Clearance values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
Urine samples were collected for urinalysis at Baseline, Weeks 2, 12, 18, 24, 48 and PT FU Weeks 4. Number of participants with shift from Baseline in urinalysis to normal (NL), abnormal (ANL) and missing (MIS) data up to Week 12 are summarized. Urine bilirubin (UBIL), urine glucose (UGLU), urine ketones (UKET), urine leukocyte esterase test (ULET) for detecting WBC, urine nitrite (UNIT), urine occult blood (UOB) were performed with dipstick method. Urine microscopy (UM) is performed to detect bacteria (BAC), red blood cells (RBC) and white blood cells (WBC). Other urinalysis parameter included urine pH (UpH) and urine specific gravity (USG). Baseline value is defined as the last Pre-treatment value observed.
The ECG parameter heart rate was measured at Baseline, Weeks 1 and 12. Change from Baseline in ECG heart rate is summarized for each post-Baseline assessment up to Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
The ECG parameters including PR interval, QRS duration, uncorrected QT interval, QTcB, QTcF were measured at Baseline, Weeks 1 and 12. Change from Baseline in ECG parameters are summarized for each post-Baseline assessment up to Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.
RVR was defined as the proportion of participants below the assay lower limit of detection (LOD) \<18 International units per milliliter (IU/mL) for Hepatitis C virus (HCV) ribonucleic acid (RNA) after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure . Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants.
RVR was defined as the proportion of participants LOD \<18 IU/mL for HCV RNA after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure. Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants. The primary and supportive analysis differs from the nominal analysis as supportive analysis is assessed at Day 28 ± 2 (2 days visit window) whereas, the nominal analysis was assessed at Day 28.
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed by nominal analysis was reported.
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed was reported.
Serum for determination of HCV genotype was collected at the screening visit. Genotype was determined by the VERSANT HCV genotype 2.0 Assay (LiPA). Number of participants with HCV genotype 1 were reported.
Blood samples for determination of HCV RNA levels were collected at immediately prior to and 1, 2, 4, 6, and 8 and 24 h after the first dose in Part 1 (Day 1). Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value. Virus RNA levels reported as \<43 are undetectable levels. If the result for HCV RNA (IU/ML) was \<43, then change from Baseline was calculated using 42, and the change from Baseline on the log scale was calculated using log (42).
AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Single 12-lead electrocardiogram (ECG) was obtained. The standard ECG criteria of potential clinical importance were 1) absolute QTc Interval, \> 450 milliseconds (msec), 2) absolute PR Interval, \<110 msec, 3) absolute QRS Interval, \< 75 msec and 4) increase from baseline in QTc \> 60 msec. QTc Interval was calculated using Frederica correction formula: QTcF = QT / (RR)\^1/3. Change from Baseline was calculated by subtracting the Baseline assessment value from post Baseline visit value. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. The change from Baseline in QTc Interval at Day 2 and 28 were reported.
| Arm | Type | Description |
|---|---|---|
| T40 | EXPERIMENTAL | Hepatitis C virus (HCV) genotype 1 GSK2336805 40 mg, pegylated interferon alpha-2a, and ribavirin arm |
| T60 | EXPERIMENTAL | Hepatitis C virus (HCV) genotype 1 GSK2336805 60 mg, pegylated interferon alpha-2a, and ribavirin arm |
| PRT | ACTIVE_COMPARATOR | Hepatitis C virus (HCV) genotype 1 Telaprevir, pegylated interferon alpha-2a, and ribavirin arm |
| G4 | EXPERIMENTAL | Hepatitis C virus (HCV) genotype 4 GSK2336805 60 mg, pegylated interferon alpha-2a, and ribavirin arm |
| GSK2336805 | EXPERIMENTAL | Study Part 1 |
| Placebo | PLACEBO_COMPARATOR | Study Part 1 |
| GSK2336805 + pegylated interferon alfa-2a + ribavrin | EXPERIMENTAL | Study Part 2 |
| Placebo + pegylated interferon alfa-2a + ribavirin | ACTIVE_COMPARATOR | Study Part 2 |
| Name | Type | Description |
|---|---|---|
| GSK2336805 40 mg | DRUG | 20 mg tablet, round, 10-mm diameter, white to off-white, no markings |
| GSK2336805 60 mg | DRUG | 30 mg tablet, round, 10-mm diameter, white to off-white, no markings |
| Pegylated interferon alpha-2a | DRUG | 180 microgram per 0.5 mL prefilled syringe for single use |
| Ribavirin | DRUG | 200-mg tablet, capsule-shaped, light blue, film-coated, and debossed with "200" on 1 side and the logo "3RP" on the other side |
| Telaprevir | DRUG | 375 mg film-coated tablet |
| GSK2336805 | DRUG | Active Investigational Drug |
| Pegylated interferon alfa-2a | DRUG | Standard of Care drug |
| GSK2336805 Matching Placebo | DRUG | Placebo of Investigational Drug |
Inclusion Criteria: * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Male or female aged 18 to 70 years of age, inclusive, at Screening. * Genotype 1 or genotype 4 hepatitis C virus (HCV) infection as assess...