Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01673178
Recruitment Status : Completed
First Posted : August 27, 2012
Results First Posted : January 14, 2015
Last Update Posted : February 16, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE August 22, 2012
First Posted Date  ICMJE August 27, 2012
Results First Submitted Date  ICMJE January 6, 2015
Results First Posted Date  ICMJE January 14, 2015
Last Update Posted Date February 16, 2015
Study Start Date  ICMJE October 2012
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2015)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last dose ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Results are reported in micro international units per milliliter (mcIU/mL).
  • 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 [ Time Frame: 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.
  • Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39 [ Time Frame: 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.
  • Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49 [ Time Frame: Day 49 ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 22, 2012)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2015)
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2012)
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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multiple Dose Study Of PF-05231023 In Adult Subjects Who Have Poor Lipid Control With And Without Type 2 Diabetes Mellitus
Official Title  ICMJE 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
Brief Summary 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Melliuts, Type 2
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * Kim AM, Somayaji VR, Dong JQ, Rolph TP, Weng Y, Chabot JR, Gropp KE, Talukdar S, Calle RA. Once-weekly administration of a long-acting fibroblast growth factor 21 analogue modulates lipids, bone turnover markers, blood pressure and body weight differently in obese people with hypertriglyceridaemia and in non-human primates. Diabetes Obes Metab. 2017 Dec;19(12):1762-1772. doi: 10.1111/dom.13023. Epub 2017 Jul 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 6, 2013)
107
Original Estimated Enrollment  ICMJE
 (submitted: August 22, 2012)
100
Actual Study Completion Date  ICMJE September 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01673178
Other Study ID Numbers  ICMJE B2901011
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date January 2015

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