Trial Outcomes & Findings for 6-week Safety and PD Study in Adults With NAFLD (NCT NCT03256526)

Last Updated: 2019-04-04

Results Overview

The percent change from baseline in whole liver fat at Week 6 was assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF). MRI-PDFF generates measures of the fraction of mobile protons in the liver attributable to fat content and provides whole liver coverage so that fat content can be assessed across 8 Couinaud liver segments. Whole liver PDFF was calculated as follows: Whole Liver PDFF= PDFFs for (Segment I+Segment II+Segment III+Segment IVa+Segment IVb+Segment V+Segment VI+Segment+VII+Segment VIII) / (number of segments assessed). The same segments were to be used at both baseline and post-baseline time points in the calculation of whole liver PDFF to derive the percent change from baseline. The values of whole liver PDFF ranges from 0 to 100 and higher values represent higher liver fat.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

Baseline and Week 6

Results posted on

2019-04-04

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo matched to PF-06835919 tablets once daily (QD) were administered orally.	PF-06835919 75 mg PF-06835919 75 mg tablets QD were administered orally.	PF-06835919 300 mg PF-06835919 300mg tablets QD were administered orally.
Overall Study STARTED	19	17	17
Overall Study COMPLETED	17	17	14
Overall Study NOT COMPLETED	2	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo matched to PF-06835919 tablets once daily (QD) were administered orally.	PF-06835919 75 mg PF-06835919 75 mg tablets QD were administered orally.	PF-06835919 300 mg PF-06835919 300mg tablets QD were administered orally.
Overall Study Adverse Event	1	0	1
Overall Study Lost to Follow-up	1	0	2

Baseline Characteristics

6-week Safety and PD Study in Adults With NAFLD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=19 Participants Placebo matched to PF-06835919 tablets once daily (QD) were administered orally.	PF-06835919 75 mg n=17 Participants PF-06835919 75 mg tablets QD were administered orally.	PF-06835919 300 mg n=17 Participants PF-06835919 300 mg tablets QD were administered orally.	Total n=53 Participants Total of all reporting groups
Age, Continuous	51.00 Years STANDARD_DEVIATION 9.67 • n=5 Participants	52.82 Years STANDARD_DEVIATION 8.17 • n=7 Participants	52.29 Years STANDARD_DEVIATION 9.26 • n=5 Participants	52.00 Years STANDARD_DEVIATION 8.94 • n=4 Participants
Age, Customized 18-44 Years	6 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants
Age, Customized 45-64 Years	13 Participants n=5 Participants	15 Participants n=7 Participants	14 Participants n=5 Participants	42 Participants n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	26 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	27 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	31 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	11 Participants n=7 Participants	7 Participants n=5 Participants	22 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	17 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	39 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age Range	53.00 Years n=5 Participants	54.00 Years n=7 Participants	54.00 Years n=5 Participants	54.00 Years n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: The efficacy analysis population was defined as all randomized participants who received at least 1 dose of randomized treatment and assessed by MRI-PDFF at Week 6.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Placebo matched to PF-06835919 tablets once daily (QD) were administered orally.	PF-06835919 75 mg n=17 Participants PF-06835919 75 mg tablets QD were administered orally.	PF-06835919 300 mg n=13 Participants PF-06835919 300mg tablets QD were administered orally.
Percent Change From Baseline in Whole Liver Fat at Week 6	-7.97 Percent Change Standard Deviation 24.521	2.84 Percent Change Standard Deviation 22.246	-25.43 Percent Change Standard Deviation 22.434

SECONDARY outcome

Timeframe: Baseline up to Day 77 (28-35 days post last dose)

Population: The safety analysis population included all participants who received at least 1 dose of investigational product.

All-causality adverse events (AEs) were any untoward medical occurrence in a study participant who administered a product or medical device, the event need not necessarily have a causal relationship with the treatment or usage. Treatment-related AEs were any untoward medical occurrence in a study participant who administered a product or medical device, the event needed to have a causal relationship with the treatment or usage. A TEAE was defined as any event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Placebo matched to PF-06835919 tablets once daily (QD) were administered orally.	PF-06835919 75 mg n=17 Participants PF-06835919 75 mg tablets QD were administered orally.	PF-06835919 300 mg n=17 Participants PF-06835919 300mg tablets QD were administered orally.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) All-causality TEAEs	5 Participants	4 Participants	5 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Treatment-related TEAEs	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 56 (Week 8)

Population: The analysis population included all participants who received at least 1 dose of investigational product and were evaluated against the criteria.

The vital sign categorical criteria included: Sitting DBP (diastolic blood pressure) millimeter of mercury (mmHg) Change \>= 20 mmHg increase Sitting SBP (systolic blood pressure) (mmHg) Change \>= 30 mmHg increase Sitting DBP (mmHg) Change \>= 20 mmHg decrease Sitting SBP (mmHg) Change \>= 30 mmHg decrease Sitting DBP (mmHg) Value \< 50 mmHg Sitting Pulse Rate (bpm) Value \< 40 bpm or Value \> 120 bpm Sitting SBP (mmHg) Value \< 90 mmHg

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Placebo matched to PF-06835919 tablets once daily (QD) were administered orally.	PF-06835919 75 mg n=17 Participants PF-06835919 75 mg tablets QD were administered orally.	PF-06835919 300 mg n=17 Participants PF-06835919 300mg tablets QD were administered orally.
Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria Sitting DBP (mmHg) Change >= 20 mmHg increase	1 Participants	0 Participants	1 Participants
Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria Sitting SBP (mmHg) Change >= 30 mmHg increase	0 Participants	0 Participants	2 Participants
Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria Sitting DBP (mmHg) Change >= 20 mmHg decrease	1 Participants	1 Participants	0 Participants
Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria Sitting SBP (mmHg) Change >= 30 mmHg decrease	0 Participants	1 Participants	2 Participants
Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria Sitting DBP (mmHg) Value <50 mmHg	0 Participants	0 Participants	0 Participants
Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria Sitting Pulse Rate (bpm) Value < 40 bpm	0 Participants	0 Participants	0 Participants
Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria Sitting Pulse Rate (bpm) Value > 120 bpm	0 Participants	0 Participants	0 Participants
Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria Sitting SBP (mmHg) Value < 90 mmHg	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 56 (Week 8)

Population: The analysis population included all participants who received at least 1 dose of investigational product and were evaluated against the criteria.

The ECG categorical criteria included: PR Interval (msec) percent (%)Change \>= 25% increase when baseline \>200 or \>=50% increase when baseline \<=200 QRS Interval (msec) %Change \>= 50% increase QTcF Interval (Fridericia's Correction) (msec) increase 30 \<= Change \< 60 or Change \>= 60 PR Interval (msec) Value \>= 300 QRS Interval (msec) Value \>= 140 QTcF Interval (Fridericia's Correction) (msec) 450 \<= Value \<480 or 480 \<=Value \<500 or Value \>= 500

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Placebo matched to PF-06835919 tablets once daily (QD) were administered orally.	PF-06835919 75 mg n=17 Participants PF-06835919 75 mg tablets QD were administered orally.	PF-06835919 300 mg n=17 Participants PF-06835919 300mg tablets QD were administered orally.
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria QTcF Interval (msec) Change >= 60 increase	0 Participants	0 Participants	0 Participants
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria PR Interval (msec) Value >= 300	0 Participants	0 Participants	0 Participants
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria QRS Interval (msec) %Change >= 50% increase	0 Participants	0 Participants	0 Participants
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria QTcF Interval (msec) 30<= Change < 60 increase	1 Participants	0 Participants	0 Participants
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria QRS Interval (msec) Value >= 140	0 Participants	0 Participants	0 Participants
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria QTcF Interval (msec) 450 <= Value <480	1 Participants	1 Participants	0 Participants
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria QTcF Interval (msec) 480<= Value < 500	0 Participants	0 Participants	0 Participants
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria QTcF Interval (msec) Value >= 500	1 Participants	0 Participants	0 Participants
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria PR Interval (msec) %Change >= 25/50% increase	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 56 (Week 8)

Population: The analysis population included participants with at least 1 observation of the given laboratory test while on study treatment.

Below parameters were evaluated for laboratory tests: Hemoglobin, Hematocrit, Erythrocytes, Ery. Mean Copuscular Volume, Ery. Mean Copuscular Hemoglobin, Ery. Mean Corpuscular HGB Concentration, Platelets, Leukocytes, Lymphocytes, Neuprophils, Basophils, Eosinophils, Monocytes, Bilirubin, Direct Biliirubin, Indirect Bilirubin, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase, Alkaline Phosphatase, Protein, Albumin, Albumin, Blood Urea Nitrogen, Creatinine, Urate, Sodium, Potassium, Chloride, Calcium, Bicarbonate, Glucose-Fasting, pH, Urine Glucose, Ketone, Urine Protein, Urine Hemoglobin, Urobilinogen, Urine Bilirubin, Nitrite, Leukocyte Esterase, Urine Erythocytes, Urine leukocytes, Hyaline Casts, Urine Creatinine.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Placebo matched to PF-06835919 tablets once daily (QD) were administered orally.	PF-06835919 75 mg n=17 Participants PF-06835919 75 mg tablets QD were administered orally.	PF-06835919 300 mg n=17 Participants PF-06835919 300mg tablets QD were administered orally.
Number of Participants With Laboratory Abnormalities	9 Participants	8 Participants	8 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

PF-06835919 75 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

PF-06835919 300 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Restriction Description: 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 disclosure previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=19 participants at risk Placebo matched to PF-06835919 tablets once daily (QD) were administered orally.	PF-06835919 75 mg n=17 participants at risk PF-06835919 75 mg tablets QD were administered orally.	PF-06835919 300 mg n=17 participants at risk PF-06835919 300 mg tablets QD were administered orally.
Eye disorders Eye pain	5.3% 1/19 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Gastrointestinal disorders Diarrhoea	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)
Gastrointestinal disorders Dyspepsia	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)
Gastrointestinal disorders Gastritis	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)
Gastrointestinal disorders Vomiting	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)
General disorders Fatigue	5.3% 1/19 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
General disorders Pain	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Infections and infestations Tooth abscess	5.3% 1/19 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Infections and infestations Upper respiratory tract infection	5.3% 1/19 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Infections and infestations Urinary tract infection	10.5% 2/19 • Number of events 2 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)
Infections and infestations Viral infection	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Metabolism and nutrition disorders Increased appetite	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)
Musculoskeletal and connective tissue disorders Back pain	5.3% 1/19 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)
Musculoskeletal and connective tissue disorders Myalgia	5.3% 1/19 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Musculoskeletal and connective tissue disorders Pain in extremity	5.3% 1/19 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Nervous system disorders Hyperaesthesia	5.3% 1/19 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Nervous system disorders Dizziness	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Renal and urinary disorders Dysuria	5.3% 1/19 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)
Skin and subcutaneous tissue disorders Rash	0.00% 0/19 • Baseline up to Day 77 (28-35 days post last dose)	0.00% 0/17 • Baseline up to Day 77 (28-35 days post last dose)	5.9% 1/17 • Number of events 1 • Baseline up to Day 77 (28-35 days post last dose)