A Multiple Oral Doses Study Of PF-06427878 In Healthy Adult Subjects

Study Overview
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Brief Summary
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PF-06427878 is a new compound proposed for the treatment of hyperlipidemia. The primary purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple oral doses of PF-06427878 in healthy adult subjects.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess The Safety, Tolerability, And Pharmacokinetics Of Multiple Escalating Oral Doses Of Pf-06427878 Co Administered With And Without Food In Healthy Adult Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: PF-06427878
* Drug: Placebo
* Drug: PF-06427878
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects of non childbearing potential. Body Mass Index (BMI) of 17.5 to 35.4 kg/m2; and a total body weight >50 kg Subjects with fasting TG level of >=90 mg/dL and <=500 mg/dL following an overnight fast Subjects with low density lipoprotein cholesterol between 115 mg/dL and 190 mg/dL following an overnight fast Exclusion Criteria: •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Single dose level of PF-06427878 at 5 mg or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06427878<br>* PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8).<br>Drug: Placebo<br>* Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).<br>|
| Experimental: Cohort 2<br>Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 1 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06427878<br>* PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8).<br>Drug: Placebo<br>* Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).<br>|
| Experimental: Cohort 3<br>Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 2 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06427878<br>* PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8).<br>Drug: Placebo<br>* Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).<br>|
| Experimental: Cohort 4<br>Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 3 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06427878<br>* PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8).<br>Drug: Placebo<br>* Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).<br>|
| Experimental: Cohort 5<br>Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 4 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06427878<br>* PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8).<br>Drug: Placebo<br>* Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).<br>|
| Experimental: Cohort 6<br>Single dose level of PF-06427878 (with the same total daily dose as Cohort 5) or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06427878<br>* PF-06427878 will be administered as an extemporaneously prepared solution every 12 hours for 14 days (n=8).<br>Drug: Placebo<br>* Placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days (n=2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse events (AEs). |  | 0-25 days | 
| Assessment of clinical laboratory tests. |  | 0-25 days | 
| Assessment of vital signs (including blood pressure and pulse rate). |  | 0-25 days | 
| Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG). |  | 0-25 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06427878during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06427878 on day 14 |  | 0, 1, 2, 3, 4, 6, 8, 12 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Plasma Decay Half-Life (t1/2) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Apparent Volume of Distribution (Vz/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Apparent Oral Clearance (CL/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Minimum Observed Plasma Concentration (Cmin) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Peak:Trough ratio of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1 |  | 0, 1, 2, 3, 4, 6, 8, 12 hours post dose | 
| Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUCtau)) for PF-06427878 on day14 relative to day 1 |  | 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose | 
| Amount of PF-06427878 excreted in urine (Ae) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0- tau hours post dose | 
| Percent of dose excreted in urine as PF-06427878 (Ae%) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0- tau hours post dose | 
| Renal clearance of PF-06427878 (CLr) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 |  | 0- tau hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Ascending Dose, Healthy Subjects, Hyperlipidemia, Lipid Metabolism Disorders, Metabolic Diseases