Multiple Dose Study Of PF-05231023 In Adult Subjects Who Have Poor Lipid Control With And Without Type 2 Diabetes Mellitus

Pfizer107 enrolled

Overview

This is a trial in obese subjects who have poor lipid control with and without Type 2 diabetes mellitus to study the safety, tolerability and pharmacokinetics of multiple doses of PF-05231023

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

107

Conditions

Diabetes Melliuts, Type 2

Interventions

PlaceboOTHER

0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), once a week for 4 weeks

25 mg PF-05231023DRUG

25 mg IV once a week for 4 weeks

50 mg PF-05231023DRUG

50 mg IV once a week for 4 weeks

Eligibility

Sex: ALLMin age: 30 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male and female subjects of non-childbearing potential between the ages of 30 and 70 years with and without a diagnosis of Type 2 diabetes mellitus (according to the American Diabetes Association guidelines). * Subjects with poor lipid control as confirmed by laboratory tests. * BMI of 30 to 40 Kg/m2 and a total body weight of \>50 kg (110 lbs). 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 asymptomatic, seasonal allergies at time of dosing). * Levels of blood enzymes indicating pancreatitis or elevated liver function enzymes outside of the laboratory's reference range as confirmed by laboratory tests. * Subjects with Type 1 Diabetes Mellitus.

Locations (17)

Anaheim Clinical Trials, LLC

Anaheim, California, United States

Profil Institute for Clinical Research, Inc.

Chula Vista, California, United States

Outcomes

Primary Outcomes

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events were between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

Time frame: Baseline up to 28 days after last dose

Number of Participants With Laboratory Abnormalities

Criteria for laboratory test abnormality: Hematology (hemoglobin, hematocrit, red blood corpuscles \[RBC\] count: less than \[\<\]0.8\*lower limit of normal \[LLN\], platelets: \<0.5\*LLN/greater than \[\>\]1.75\*upper limit of normal \[ULN\], leukocytes: \<0.6\*LLN or \>1.5\*ULN, lymphocytes, total neutrophils: \<0.8\*LLN or \>1.2\*ULN, basophils, eosinophil: \<0.8\*LLN, monocytes: \>1.2\*ULN); Liver Function (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: \>0.3\*ULN, total protein, albumin: \<0.8\*LLN or \>1.2\*ULN); total bilirubin, direct bilirubin, indirect bilirubin: \>1.5\*ULN; Renal Function (blood urea nitrogen, creatinine: \>1.3\*ULN, uric acid: \>1.2\*ULN); Electrolytes (sodium: \<0.95\*LLN or \>1.05\*ULN, potassium, chloride, calcium, bicarbonate: \<0.9\*LLN or \>1.1\*ULN; creatine kinase: \>2.0\*ULN; glucose fasting: \<0.6\*LLN or \>1.5\*ULN, urine white blood corpuscles \[WBC\] and RBC: greater than or equal to (\>=) 20/High Power Field \[HPF\]).

Time frame: Baseline up to Day 49

Number of Participants With Clinically Significant Vital Sign Abnormalities

Criteria for clinically significant vital signs abnormalities included supine/sitting pulse rate of \<40 beats per minute (bpm) or \>120 bpm, supine systolic blood pressure (SBP) of \<90 millimeter of mercury (mmHg), \>=30 mmHg maximum increase and decrease from baseline in same posture, supine diastolic blood pressure (DBP) of \<50 mmHg; \>=20 mmHg maximum increase and decrease from baseline in same posture.

Data from ClinicalTrials.gov

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100 mg IV once a week for 4 weeks

150 mg PF-05231023DRUG

150 mg IV once a week for 4 weeks

Diablo Clinical Research, Inc.

Walnut Creek, California, United States

Avail Clinical Research, LLC

DeLand, Florida, United States

Elite Research Institute

Miami, Florida, United States

Miami Research Associates, Inc.

South Miami, Florida, United States

MRA Clinical Research, LLC

South Miami, Florida, United States

Central Kentucky Research Associates, Inc.

Lexington, Kentucky, United States

L-MARC Research Center

Louisville, Kentucky, United States

Prism Research

Saint Paul, Minnesota, United States

...and 7 more locations

Time frame: Baseline up to Day 49

Number of Participants With Clinically Significant Electrocardiogram Findings

Clinically significant ECG findings included PR interval \>=300 milliseconds (msec) or \>=25 percent (%) increase from baseline (if baseline PR interval \>200 msec) or \>=50% increase (if baseline PR interval less than or equal to \[\<=\] 200 msec); QRS interval \>=140 msec or \>=50% increase from baseline; QT interval \>=500 msec, corrected QT interval based on Fridericia's formula (QTcF) 450 to \<480 msec, 480 to \<500 msec, \>=500 msec or \>=30 msec but \<60 msec increase from baseline or \>=60 msec increase from baseline.

Time frame: Baseline up to Day 49

Number of Participants With Abnormal Physical Examinations

Physical examination included general examination and examination of head, ears, eyes, nose, mouth, throat, neck, abdomen, skin, heart, lungs, lymph nodes, and gastrointestinal and musculoskeletal and neurological system.

Time frame: Baseline up to Day 49

Thyroid Stimulating Hormone (TSH) Level at Baseline

Results are reported in micro international units per milliliter (mcIU/mL).

Time frame: Baseline

Thyroid Stimulating Hormone (TSH) Level at Day 1

Time frame: Day 1

Thyroid Stimulating Hormone (TSH) Level at Day 25

Time frame: Day 25

Thyroid Stimulating Hormone (TSH) Level at Day 39

Time frame: Day 39

Thyroid Stimulating Hormone (TSH) Level at Day 49

Time frame: Day 49

Phosphate Level at Baseline

Time frame: Baseline

Change From Baseline in Phosphate Level at Day 8

Time frame: Baseline, Day 8

Change From Baseline in Phosphate Level at Day 15

Time frame: Baseline, Day 15

Change From Baseline in Phosphate Level at Day 25

Time frame: Baseline, Day 25

Change From Baseline in Phosphate Level at Day 49

Time frame: Baseline, Day 49

Creatine Phosphokinase (CPK) Level at Baseline

Time frame: Baseline

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8

Time frame: Baseline, Day 8

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15

Time frame: Baseline, Day 15

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25

Time frame: Baseline, Day 25

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49

Time frame: Baseline, Day 49

Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline

Time frame: Baseline

Percent Change From Baseline in Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Day 25

Time frame: Baseline, Day 25

Percent Change From Baseline in Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Day 39

Time frame: Baseline, Day 39

Percent Change From Baseline Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Day 49

Time frame: Baseline, Day 49

Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline

Time frame: Baseline

Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25

Time frame: Baseline, Day 25

Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39

Time frame: Baseline, Day 39

Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49

Time frame: Baseline, Day 49

Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline

Time frame: Baseline

Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25

Time frame: Baseline, Day 25

Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39

Time frame: Baseline, Day 39

Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49

Time frame: Day 49

Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline

Time frame: Baseline

Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24

Time frame: Day 24

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1

Anti-PF-05231023 antibodies and neutralizing antibodies were analyzed only for participants who received PF-05231023 as per planned analysis. One sample at Day 1 was inadvertently tested for neutralizing antibody even though the corresponding anti-PF-05231023 antibody was negative.

Time frame: Day 1

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39

Anti-PF-05231023 antibodies and neutralizing antibodies were analyzed only for participants who received PF-05231023 as per planned analysis. One sample at Day 39 was inadvertently tested for neutralizing antibody even though the corresponding anti-PF-05231023 antibody was negative.

Time frame: Day 39

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49

Time frame: Day 49

Secondary Outcomes

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose

AUCtau was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1, Day 4, 0 hours (pre-dose) on Day 8

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose

Tmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1, Day 4, 0 hour (pre-dose) on Day 8

Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose

Cmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1, Day 4, 0 hour (pre-dose) on Day 8

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023

Rac was obtained from AUCtau after last dose (Day 22) divided by AUCtau after single dose (Day 1). Rac was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion ), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1; Day 4, 0 hour (pre-dose) on Day 8; 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22; Day 24, 25, 29

Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023

Time frame: 0 (pre-dose),0.5(end of infusion), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1; Day 4, 0 hour (pre-dose) on Day 8; 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22; Day 24,25,29,39,49

Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose

Cmin was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose

Cav was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Plasma Decay Half-Life (t1/2) of PF-05231023

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-Life was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Apparent Clearance (CL) of PF-05231023

CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49