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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01673178
First received: August 22, 2012
Last updated: January 28, 2015
Last verified: January 2015
  Purpose

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


Condition Intervention Phase
Diabetes Melliuts, Type 2
Other: Placebo
Drug: 25 mg PF-05231023
Drug: 50 mg PF-05231023
Drug: 100 mg PF-05231023
Drug: 150 mg PF-05231023
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1, Placebo-controlled, Randomized Trial To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Iv Doses Of Pf-05231023 In Obese Hyperlipidemic Adult Subjects With And Without Type 2 Diabetes Mellitus On A Background Of Atorvastatin

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last dose ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to Day 49 ] [ Designated as safety issue: Yes ]
    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]).

  • Number of Participants With Clinically Significant Vital Sign Abnormalities [ Time Frame: Baseline up to Day 49 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinically Significant Electrocardiogram Findings [ Time Frame: Baseline up to Day 49 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Abnormal Physical Examinations [ Time Frame: Baseline up to Day 49 ] [ Designated as safety issue: Yes ]
    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.

  • Thyroid Stimulating Hormone (TSH) Level at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    Results are reported in micro international units per milliliter (mcIU/mL).

  • Thyroid Stimulating Hormone (TSH) Level at Day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
  • Thyroid Stimulating Hormone (TSH) Level at Day 25 [ Time Frame: Day 25 ] [ Designated as safety issue: Yes ]
  • Thyroid Stimulating Hormone (TSH) Level at Day 39 [ Time Frame: Day 39 ] [ Designated as safety issue: Yes ]
  • Thyroid Stimulating Hormone (TSH) Level at Day 49 [ Time Frame: Day 49 ] [ Designated as safety issue: Yes ]
  • Phosphate Level at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Phosphate Level at Day 8 [ Time Frame: Baseline, Day 8 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Phosphate Level at Day 15 [ Time Frame: Baseline, Day 15 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Phosphate Level at Day 25 [ Time Frame: Baseline, Day 25 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Phosphate Level at Day 49 [ Time Frame: Baseline, Day 49 ] [ Designated as safety issue: Yes ]
  • Creatine Phosphokinase (CPK) Level at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8 [ Time Frame: Baseline, Day 8 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15 [ Time Frame: Baseline, Day 15 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25 [ Time Frame: Baseline, Day 25 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49 [ Time Frame: Baseline, Day 49 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25 [ Time Frame: Baseline, Day 25 ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39 [ Time Frame: Baseline, Day 39 ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49 [ Time Frame: Baseline, Day 49 ] [ Designated as safety issue: Yes ]
  • Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25 [ Time Frame: Baseline, Day 25 ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39 [ Time Frame: Baseline, Day 39 ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49 [ Time Frame: Day 49 ] [ Designated as safety issue: Yes ]
  • Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24 [ Time Frame: Day 24 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39 [ Time Frame: Day 39 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49 [ Time Frame: Day 49 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose [ 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 ] [ Designated as safety issue: No ]
    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 to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose [ 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 ] [ Designated as safety issue: No ]
    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.

  • Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose [ 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Minimum Observed Plasma Trough Concentration (Cmin) 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 ] [ Designated as safety issue: No ]
    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.

  • Average Plasma Concentration (Cav ) of PF-05231023 After the 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 ] [ Designated as safety issue: No ]
    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.

  • Plasma Decay Half-Life (t1/2) of PF-05231023 [ 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 ] [ Designated as safety issue: No ]
    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.

  • Apparent Clearance (CL) of PF-05231023 [ 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 107
Study Start Date: October 2012
Study Completion Date: September 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Arm Other: Placebo
0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), once a week for 4 weeks
Experimental: 25 mg Drug: 25 mg PF-05231023
25 mg IV once a week for 4 weeks
Experimental: 50 mg Drug: 50 mg PF-05231023
50 mg IV once a week for 4 weeks
Experimental: 100 mg Drug: 100 mg PF-05231023
100 mg IV once a week for 4 weeks
Experimental: 150 mg Drug: 150 mg PF-05231023
150 mg IV once a week for 4 weeks

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673178

Locations
United States, California
Anaheim Clinical Trials, LLC
Anaheim, California, United States, 92801
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States, 91911
Diablo Clinical Research, Inc.
Walnut Creek, California, United States, 94598
United States, Florida
Avail Clinical Research, LLC
DeLand, Florida, United States, 32720
Elite Research Institute
Miami, Florida, United States, 33169
Miami Research Associates, Inc.
South Miami, Florida, United States, 33143
MRA Clinical Research, LLC
South Miami, Florida, United States, 33143
United States, Kentucky
Central Kentucky Research Associates, Inc.
Lexington, Kentucky, United States, 40509
L-MARC Research Center
Louisville, Kentucky, United States, 40213
United States, Minnesota
Prism Research
Saint Paul, Minnesota, United States, 55114
United States, North Carolina
High Point Clinical Trials Center, LLC
High Point, North Carolina, United States, 27265
Carolina Phase 1 Research
Raleigh, North Carolina, United States, 27612
Wake Internal Medicine Consultants
Raleigh, North Carolina, United States, 27612
United States, Ohio
Community Research
Cincinnati, Ohio, United States, 45255
Medpace Clinical Pharmacology Unit
Cincinnati, Ohio, United States, 45227
Mercy Hospital Pharmacy
Cincinnati, Ohio, United States, 45255
United States, Texas
Covance Clinical Research Unit
Dallas, Texas, United States, 75247
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01673178     History of Changes
Other Study ID Numbers: B2901011
Study First Received: August 22, 2012
Results First Received: January 6, 2015
Last Updated: January 28, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Type 2 diabetes
safety
multiple dose
intravenous

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on May 03, 2015