Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

August 22, 2012
January 28, 2015
October 2012
August 2013   (final data collection date for primary outcome measure)
  • 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 ]
Evaluate the safety and tolerability of multiple intravenous doses of PF-05231023 administered once weekly to obese adult subjects with hypertriglyceridemia with and without Type 2 diabetes mellitus (T2DM). [ Time Frame: 27 Days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01673178 on ClinicalTrials.gov Archive Site
  • 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.
Characterize the pharmacokinetics of PF-05231023 after multiple intravenous doses administered once weekly to obese adult subjects with hypertriglyceridemia with and without Type 2 diabetes mellitus (T2DM). [ Time Frame: 27 Days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Multiple Dose Study Of PF-05231023 In Adult Subjects Who Have Poor Lipid Control With And Without Type 2 Diabetes Mellitus
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

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

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Diabetes Melliuts, Type 2
  • Other: Placebo
    0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), once a week for 4 weeks
  • Drug: 25 mg PF-05231023
    25 mg IV once a week for 4 weeks
  • Drug: 50 mg PF-05231023
    50 mg IV once a week for 4 weeks
  • Drug: 100 mg PF-05231023
    100 mg IV once a week for 4 weeks
  • Drug: 150 mg PF-05231023
    150 mg IV once a week for 4 weeks
  • Placebo Comparator: Placebo Arm
    Intervention: Other: Placebo
  • Experimental: 25 mg
    Intervention: Drug: 25 mg PF-05231023
  • Experimental: 50 mg
    Intervention: Drug: 50 mg PF-05231023
  • Experimental: 100 mg
    Intervention: Drug: 100 mg PF-05231023
  • Experimental: 150 mg
    Intervention: Drug: 150 mg PF-05231023
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
107
September 2013
August 2013   (final data collection date for primary outcome measure)

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.
Both
30 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01673178
B2901011
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP