Trial Outcomes & Findings for Safety And Efficacy Of Oral PF-4136309 In Patients With Chronic Hepatitis C Infection And Abnormal Liver Enzymes (NCT NCT01226797)

NCT ID: NCT01226797

Last Updated: 2023-07-27

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 24 participants
• Primary outcome timeframe: Week 4
• Results posted on: 2023-07-27

Participant Flow

Participant milestones

Measure	PF-04136309 PF-04136309 administered orally as four 125 milligram (mg) capsules twice daily for up to 4 weeks.	Placebo PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Overall Study STARTED	12	12
Overall Study COMPLETED	10	11
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	PF-04136309 PF-04136309 administered orally as four 125 milligram (mg) capsules twice daily for up to 4 weeks.	Placebo PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Overall Study Adverse Event	1	0
Overall Study No longer willing to participate	1	0
Overall Study Protocol Violation	0	1

Baseline Characteristics

Safety And Efficacy Of Oral PF-4136309 In Patients With Chronic Hepatitis C Infection And Abnormal Liver Enzymes

Baseline characteristics by cohort

Measure	PF-04136309 n=12 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=12 Participants PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.	Total n=24 Participants Total of all reporting groups
Age, Customized 18 to 44 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age, Customized 45 to 64 years	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 4

Population: 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).

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.

Outcome measures

Measure	PF-04136309 n=12 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=11 Participants PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Percentage of Participants With a Response in Serum Alanine Aminotransferase (ALT) Level at Week 4	25.00 Percentage of participants	36.36 Percentage of participants

SECONDARY outcome

Timeframe: Week 4

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF.

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.

Outcome measures

Measure	PF-04136309 n=12 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=11 Participants PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Percentage of Participants With a Response in Serum Aspartate Aminotransferase (AST) Level From Baseline at Week 4	8.33 Percentage of participants	36.36 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3 and 4

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF.

Baseline ALT value was defined as mean of measurements collected at screening visits 1 and 2 and pre-dose Day 1.

Outcome measures

Measure	PF-04136309 n=12 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=11 Participants PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Change From Baseline in Serum ALT at Weeks 1, 2, 3 and 4 Change at Week 1	11.75 International units per liter Interval -11.08 to 34.58	-13.70 International units per liter Interval -37.56 to 10.16
Change From Baseline in Serum ALT at Weeks 1, 2, 3 and 4 Change at Week 2	-9.40 International units per liter Interval -28.75 to 9.94	-22.89 International units per liter Interval -43.11 to -2.68
Change From Baseline in Serum ALT at Weeks 1, 2, 3 and 4 Change at Week 3	-9.90 International units per liter Interval -34.77 to 14.97	-25.08 International units per liter Interval -51.07 to 0.92
Change From Baseline in Serum ALT at Weeks 1, 2, 3 and 4 Change at Week 4	-8.25 International units per liter Interval -35.36 to 18.85	-32.87 International units per liter Interval -61.2 to -4.54

SECONDARY outcome

Timeframe: Baseline

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value; Observed data

Baseline ALT level was defined as the mean of measurements collected on Screening visits 1 and 2 and pre-dose Day 1.

Outcome measures

Measure	PF-04136309 n=12 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=11 Participants PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Serum ALT at Baseline	132.2 International units per liter Standard Deviation 61.57	154.7 International units per liter Standard Deviation 81.47

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3 and 4

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF.

Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1.

Outcome measures

Measure	PF-04136309 n=12 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=11 Participants PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Change From Baseline in Serum AST at Weeks 1, 2, 3 and 4 Change at Week 1	5.90 International units per liter Interval -9.68 to 21.47	-15.98 International units per liter Interval -32.25 to 0.3
Change From Baseline in Serum AST at Weeks 1, 2, 3 and 4 Change at Week 2	-5.60 International units per liter Interval -20.04 to 8.84	-14.89 International units per liter Interval -29.98 to 0.2
Change From Baseline in Serum AST at Weeks 1, 2, 3 and 4 Change at Week 3	-1.65 International units per liter Interval -18.64 to 15.33	-15.74 International units per liter Interval -33.49 to 2.01
Change From Baseline in Serum AST at Weeks 1, 2, 3 and 4 Change at Week 4	5.22 International units per liter Interval -17.48 to 27.93	-23.97 International units per liter Interval -47.7 to -0.24

SECONDARY outcome

Timeframe: Baseline

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value; Observed data

Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1.

Outcome measures

Measure	PF-04136309 n=12 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=11 Participants PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Serum AST at Baseline	96.6 International units per liter Standard Deviation 47.29	110.6 International units per liter Standard Deviation 48.47

SECONDARY outcome

Timeframe: Baseline, Weeks 1 and 4

Population: Data for this outcome measure was not collected because there was a change in planned analysis owing to low enrolment number in the study.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Data for this outcome measure was not collected because there was a change in planned analysis owing to low enrolment number in the study.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28

Population: 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.

Cmax was defined as maximum observed plasma concentration of PF-04136309.

Outcome measures

Measure	PF-04136309 n=11 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Maximum Observed Plasma Concentration (Cmax) of PF-04136309	3448 Nanogram per milliliter Standard Deviation 1098.8	—

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28

Population: 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.

Plasma decay half-life was the time measured for the plasma concentration to decrease by one half.

Outcome measures

Measure	PF-04136309 n=10 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Plasma Decay Half-Life (t1/2) of PF-04136309	14.71 Hours Standard Deviation 1.4594	—

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28

Population: 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.

AUCtau was defined as area under the concentration curve from time zero to end of dosing interval of PF-04136309.

Outcome measures

Measure	PF-04136309 n=10 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04136309	12940 Nanograms*hour per milliliter Standard Deviation 6945.8	—

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28

Population: 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.

Tmax was defined as time to reach maximum observed plasma concentration of PF-04136309.

Outcome measures

Measure	PF-04136309 n=11 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04136309	0.500 Hours Interval 0.5 to 2.0	—

SECONDARY outcome

Timeframe: Baseline, Week 2 and 4

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF.

p-ERK is a biomarker used to assess bioavailability of PF-04136309. Baseline p-ERK level defined as the last pre-dose measurement.

Outcome measures

Measure	PF-04136309 n=12 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=11 Participants PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Change From Baseline in Phosphorylated Extracellular Signal- Regulated Kinase (p-ERK) Levels at Week 2 and 4 Change at Week 2	-19.00 Percentage of p-ERK Interval -28.54 to -9.46	3.06 Percentage of p-ERK Interval -6.49 to 12.6
Change From Baseline in Phosphorylated Extracellular Signal- Regulated Kinase (p-ERK) Levels at Week 2 and 4 Change at Week 4	-19.39 Percentage of p-ERK Interval -25.79 to -12.99	-3.05 Percentage of p-ERK Interval -9.74 to 3.63

SECONDARY outcome

Timeframe: Baseline

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value; Observed data

p-ERK is a biomarker used to assess bioavailability of PF-04136309. Baseline p-ERK level defined as the last pre-dose measurement.

Outcome measures

Measure	PF-04136309 n=12 Participants PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=11 Participants PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Baseline p-ERK	29.63 Percentage of p-ERK Standard Deviation 24.451	23.94 Percentage of p-ERK Standard Deviation 16.435

Adverse Events

PF-04136309

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	PF-04136309 n=12 participants at risk PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=12 participants at risk PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Cardiac disorders Sinus bradycardia	8.3% 1/12 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.	0.00% 0/12 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.
Injury, poisoning and procedural complications Hand fracture	8.3% 1/12 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.	0.00% 0/12 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.

Other adverse events

Measure	PF-04136309 n=12 participants at risk PF-04136309 administered orally as four 125 mg capsules twice daily for up to 4 weeks.	Placebo n=12 participants at risk PF-04136309 matched placebo capsules administered as four capsules twice daily for up to 4 weeks.
Gastrointestinal disorders Abdominal discomfort	16.7% 2/12 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.	8.3% 1/12 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.
Gastrointestinal disorders Constipation	8.3% 1/12 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.	0.00% 0/12 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.
Gastrointestinal disorders Epigastric discomfort	8.3% 1/12 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.	0.00% 0/12 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.
Gastrointestinal disorders Nausea	16.7% 2/12 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.	0.00% 0/12 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.
General disorders Asthenia	0.00% 0/12 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.	8.3% 1/12 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.
General disorders Fatigue	0.00% 0/12 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.	8.3% 1/12 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.
General disorders Oedema	0.00% 0/12 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.	8.3% 1/12 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.
Infections and infestations Cystitis	8.3% 1/12 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.	0.00% 0/12 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.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 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.	0.00% 0/12 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.
Nervous system disorders Dizziness	50.0% 6/12 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.	0.00% 0/12 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.
Psychiatric disorders Insomnia	0.00% 0/12 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.	8.3% 1/12 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.
Skin and subcutaneous tissue disorders Acne	8.3% 1/12 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.	0.00% 0/12 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.
Skin and subcutaneous tissue disorders Urticaria	8.3% 1/12 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.	0.00% 0/12 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.
Vascular disorders Hot flush	8.3% 1/12 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.	0.00% 0/12 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.

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER