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See termination reason in detailed description.
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This study will evaluate the effect of PF-04136309 in patients with chronic hepatitic C virus infection and abnormal liver enzymes.
Study recruitment was stopped on Dec 15, 2011 due to difficulty in enrolling the targeted number of patients. Subjects currently enrolled into the study will complete the study as per protocol. There were no safety concerns involved in the decision to stop enrollment. The new anticipated Last Subject Last Visit (LSLV) is February 2012.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| PF-04136309 | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Take 4 capsules twice daily 12 hours apart with water. Swallow whole. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With a Response in Serum Alanine Aminotransferase (ALT) Level at Week 4 | Responder was defined as a participant who experienced reduction in ALT of greater than or equal to (>=) 30 percent (%) of the baseline value. Baseline ALT value was defined as mean of measurements collected at screening visits 1 and 2 and pre-dose Day 1. ALT levels were determined at central lab. | Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With a Response in Serum Aspartate Aminotransferase (AST) Level From Baseline at Week 4 | AST responder status was defined as a reduction in AST >= 30% of the baseline value and or normalization. Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1. AST levels were determined at central lab. | Week 4 |
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Inclusion Criteria:
Exclusion Criteria:
Prior liver biopsy showing cirrhosis.
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Chinese University of Hong Kong, | Prince of Wales Hospital, Shatin, New Territories, | Hong Kong | 0 | Hong Kong | ||
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-04136309 | PF-04136309 administered orally as four 125 milligram (mg) capsules twice daily for up to 4 weeks. |
| FG001 | Placebo | PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | PF-04136309 | PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks. |
| BG001 | Placebo | PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With a Response in Serum Alanine Aminotransferase (ALT) Level at Week 4 | Responder was defined as a participant who experienced reduction in ALT of greater than or equal to (>=) 30 percent (%) of the baseline value. Baseline ALT value was defined as mean of measurements collected at screening visits 1 and 2 and pre-dose Day 1. ALT levels were determined at central lab. | Full Analysis Set (FAS): all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using last observation carried forward (LOCF). | Posted | Number | Percentage of participants | Week 4 |
|
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The same event may appear as both an adverse events (AE) and a serious adverse events (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-04136309 | PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus bradycardia | Cardiac disorders | MedDRA 14.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
Study recruitment stopped early due to difficulty in enrolling enough participants. Study terminated early due to a recommendation to terminate further development of PF-04136309 in this indication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| ID | Term |
|---|---|
| D019698 | Hepatitis C, Chronic |
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| C000620181 | PF-04136309 |
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| PF-04136309 |
| Drug |
Take 4 capsules twice daily 12 hours apart with water. Swallow whole. |
|
| Change From Baseline in Serum ALT at Weeks 1, 2, 3 and 4 | Baseline ALT value was defined as mean of measurements collected at screening visits 1 and 2 and pre-dose Day 1. | Baseline, Weeks 1, 2, 3 and 4 |
| Serum ALT at Baseline | Baseline ALT level was defined as the mean of measurements collected on Screening visits 1 and 2 and pre-dose Day 1. | Baseline |
| Change From Baseline in Serum AST at Weeks 1, 2, 3 and 4 | Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1. | Baseline, Weeks 1, 2, 3 and 4 |
| Serum AST at Baseline | Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1. | Baseline |
| Change From Baseline in Methacetin Breath Test (BreathID) at Weeks 1 and 4 | After drinking 13ˆC-methacetin, participants breath was collected using a BreathID® collection system for approximately 60 minutes and the ratio of 13ˆCO2:12ˆCO2 were determined to monitor the function of the liver. Results to be reported in ratio. | Baseline, Weeks 1 and 4 |
| Change From Baseline in Enhanced Liver Fibrosis Test (ELF) at Week 4 | Markers of fibrosis assessed in the ELF test comprise hyaluronic acid (HA), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), and amino terminal peptide of pro-collagen III (PIIINP). The HA ranges from 0 to 1000 in ng/mL; the TIMP-1 ranges from 0 to 3000 ng/mL; and the PIIINP tissue ranges from 0 to 151 in nanograms/milliliter (ng/mL). ELF algorithm calculates a discriminant score (DS) specified by DS = -7.412 plus (+) 0.681 times (*)ln(HA)+ 0.494 * ln(TIMP1)+ 0.775 * ln(PIIINP). Results to be reported in discriminant score. | Baseline, Week 4 |
| Maximum Observed Plasma Concentration (Cmax) of PF-04136309 | Cmax was defined as maximum observed plasma concentration of PF-04136309. | Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28 |
| Plasma Decay Half-Life (t1/2) of PF-04136309 | Plasma decay half-life was the time measured for the plasma concentration to decrease by one half. | Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28 |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04136309 | AUCtau was defined as area under the concentration curve from time zero to end of dosing interval of PF-04136309. | Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28 |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04136309 | Tmax was defined as time to reach maximum observed plasma concentration of PF-04136309. | Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28 |
| Change From Baseline in Phosphorylated Extracellular Signal- Regulated Kinase (p-ERK) Levels at Week 2 and 4 | p-ERK is a biomarker used to assess bioavailability of PF-04136309. Baseline p-ERK level defined as the last pre-dose measurement. | Baseline, Week 2 and 4 |
| Baseline p-ERK | p-ERK is a biomarker used to assess bioavailability of PF-04136309. Baseline p-ERK level defined as the last pre-dose measurement. | Baseline |
| The University of Hong Kong, |
| Hong Kong |
| 0 |
| Hong Kong |
| Manipal Hospital | Bangalore | Karnataka | 560017 | India |
| Seth G. S. Medical College & King Edward Memorial Hospital, | Mumbai | Maharashtra | 400 012 | India |
| Institute of Liver & Biliary Sciences | New Delhi | 110 070 | India |
| Singapore General Hospital | Singapore | 169608 | Singapore |
| Seoul National University Hospital, Department of Internal Medicine | Seoul | 110-744 | South Korea |
| Severance Hospital, Yonsei University College of Medicine, Division of Gastroenterology | Seoul | 120-752 | South Korea |
| Chung-Ho Memorial Hospital, Kaohsiung Medical University | Kaohsiung City | 807 | Taiwan |
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| Protocol Violation |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Placebo |
PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks. |
|
|
|
| Secondary | Percentage of Participants With a Response in Serum Aspartate Aminotransferase (AST) Level From Baseline at Week 4 | AST responder status was defined as a reduction in AST >= 30% of the baseline value and or normalization. Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1. AST levels were determined at central lab. | FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF. | Posted | Number | Percentage of participants | Week 4 |
|
|
|
|
| Secondary | Change From Baseline in Serum ALT at Weeks 1, 2, 3 and 4 | Baseline ALT value was defined as mean of measurements collected at screening visits 1 and 2 and pre-dose Day 1. | FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF. | Posted | Least Squares Mean | 95% Confidence Interval | International units per liter | Baseline, Weeks 1, 2, 3 and 4 |
|
|
|
|
| Secondary | Serum ALT at Baseline | Baseline ALT level was defined as the mean of measurements collected on Screening visits 1 and 2 and pre-dose Day 1. | FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value; Observed data | Posted | Mean | Standard Deviation | International units per liter | Baseline |
|
|
|
| Secondary | Change From Baseline in Serum AST at Weeks 1, 2, 3 and 4 | Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1. | FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF. | Posted | Least Squares Mean | 95% Confidence Interval | International units per liter | Baseline, Weeks 1, 2, 3 and 4 |
|
|
|
|
| Secondary | Serum AST at Baseline | Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1. | FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value; Observed data | Posted | Mean | Standard Deviation | International units per liter | Baseline |
|
|
|
| Secondary | Change From Baseline in Methacetin Breath Test (BreathID) at Weeks 1 and 4 | After drinking 13ˆC-methacetin, participants breath was collected using a BreathID® collection system for approximately 60 minutes and the ratio of 13ˆCO2:12ˆCO2 were determined to monitor the function of the liver. Results to be reported in ratio. | Data for this outcome measure was not collected because there was a change in planned analysis owing to low enrolment number in the study. | Posted | Baseline, Weeks 1 and 4 |
|
|
| Secondary | Change From Baseline in Enhanced Liver Fibrosis Test (ELF) at Week 4 | Markers of fibrosis assessed in the ELF test comprise hyaluronic acid (HA), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), and amino terminal peptide of pro-collagen III (PIIINP). The HA ranges from 0 to 1000 in ng/mL; the TIMP-1 ranges from 0 to 3000 ng/mL; and the PIIINP tissue ranges from 0 to 151 in nanograms/milliliter (ng/mL). ELF algorithm calculates a discriminant score (DS) specified by DS = -7.412 plus (+) 0.681 times (*)ln(HA)+ 0.494 * ln(TIMP1)+ 0.775 * ln(PIIINP). Results to be reported in discriminant score. | Data for this outcome measure was not collected because there was a change in planned analysis owing to low enrolment number in the study. | Posted | Baseline, Week 4 |
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) of PF-04136309 | Cmax was defined as maximum observed plasma concentration of PF-04136309. | Pharmacokinetic (PK) parameter analysis set included all enrolled participants treated and who had at least 1 of the PK parameters of interest. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Standard Deviation | Nanogram per milliliter | Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28 |
|
|
|
| Secondary | Plasma Decay Half-Life (t1/2) of PF-04136309 | Plasma decay half-life was the time measured for the plasma concentration to decrease by one half. | PK parameter analysis set included all enrolled participants treated and who had at least 1 of the PK parameters of interest. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Hours | Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28 |
|
|
|
| Secondary | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04136309 | AUCtau was defined as area under the concentration curve from time zero to end of dosing interval of PF-04136309. | PK parameter analysis set included all enrolled participants treated and who had at least 1 of the PK parameters of interest. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Standard Deviation | Nanograms*hour per milliliter | Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28 |
|
|
|
| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04136309 | Tmax was defined as time to reach maximum observed plasma concentration of PF-04136309. | PK parameter analysis set included all enrolled participants treated and who had at least 1 of the PK parameters of interest. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure. | Posted | Median | Full Range | Hours | Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28 |
|
|
|
| Secondary | Change From Baseline in Phosphorylated Extracellular Signal- Regulated Kinase (p-ERK) Levels at Week 2 and 4 | p-ERK is a biomarker used to assess bioavailability of PF-04136309. Baseline p-ERK level defined as the last pre-dose measurement. | FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF. | Posted | Least Squares Mean | 95% Confidence Interval | Percentage of p-ERK | Baseline, Week 2 and 4 |
|
|
|
|
| Secondary | Baseline p-ERK | p-ERK is a biomarker used to assess bioavailability of PF-04136309. Baseline p-ERK level defined as the last pre-dose measurement. | FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value; Observed data | Posted | Mean | Standard Deviation | Percentage of p-ERK | Baseline |
|
|
|
| 2 |
| 12 |
| 8 |
| 12 |
| EG001 | Placebo | PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks. | 0 | 12 | 3 | 12 |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 14.1 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Epigastric discomfort | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Oedema | General disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 14.1 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Change at Week 3 |
|
| Change at Week 4 |
|
| ANCOVA |
| 0.3297 |
Treatment as fixed effect and baseline as covariate. |
| Mean Difference (Final Values) |
| 13.49 |
| 2-Sided |
| 95 |
| -14.67 |
| 41.66 |
| Superiority or Other (legacy) |
| At Week 3 | ANCOVA | 0.3925 | Treatment as fixed effect and baseline as covariate. | Mean Difference (Final Values) | 15.17 | 2-Sided | 95 | -21.04 | 51.39 | Superiority or Other (legacy) |
| At Week 4 | ANCOVA | 0.2080 | Treatment as fixed effect and baseline as covariate. | Mean Difference (Final Values) | 24.62 | 2-Sided | 95 | -14.85 | 64.09 | Superiority or Other (legacy) |
| Change at Week 3 |
|
| Change at Week 4 |
|
| ANCOVA |
| 0.3669 |
Treatment as fixed effect and baseline as covariate. |
| Mean Difference (Final Values) |
| 9.30 |
| 2-Sided |
| 95 |
| -11.71 |
| 30.30 |
| Superiority or Other (legacy) |
| At Week 3 | ANCOVA | 0.2482 | Treatment as fixed effect and baseline as covariate. | Mean Difference (Final Values) | 14.09 | 2-Sided | 95 | -10.62 | 38.80 | Superiority or Other (legacy) |
| At Week 4 | ANCOVA | 0.0801 | Treatment as fixed effect and baseline as covariate. | Mean Difference (Final Values) | 29.19 | 2-Sided | 95 | -3.84 | 62.22 | Superiority or Other (legacy) |
| ANCOVA |
| 0.0015 |
Treatment as fixed effect and baseline as covariate. |
| Mean Difference (Final Values) |
| -16.34 |
| 2-Sided |
| 95 |
| -25.64 |
| -7.04 |
| Superiority or Other (legacy) |