Clinical trial NCT01673178: Multiple Dose Study Of PF-05231023 In Adult Subjects Who Have Poor Lipid Control With And Without Type 2 Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Melliuts, Type 2
Keywords: Type 2 diabetes
safety
multiple dose
intravenous
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-08-27
Enrollment: 107
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 28 days after last dose
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to Day 49
measure: Number of Participants With Clinically Significant Vital Sign Abnormalities
timeFrame: Baseline up to Day 49
measure: Number of Participants With Clinically Significant Electrocardiogram Findings
timeFrame: Baseline up to Day 49
measure: Number of Participants With Abnormal Physical Examinations
timeFrame: Baseline up to Day 49
measure: Thyroid Stimulating Hormone (TSH) Level at Baseline
timeFrame: Baseline
measure: Thyroid Stimulating Hormone (TSH) Level at Day 1
timeFrame: Day 1
measure: Thyroid Stimulating Hormone (TSH) Level at Day 25
timeFrame: Day 25
measure: Thyroid Stimulating Hormone (TSH) Level at Day 39
timeFrame: Day 39
measure: Thyroid Stimulating Hormone (TSH) Level at Day 49
timeFrame: Day 49
measure: Phosphate Level at Baseline
timeFrame: Baseline
measure: Change From Baseline in Phosphate Level at Day 8
timeFrame: Baseline, Day 8
measure: Change From Baseline in Phosphate Level at Day 15
timeFrame: Baseline, Day 15
measure: Change From Baseline in Phosphate Level at Day 25
timeFrame: Baseline, Day 25
measure: Change From Baseline in Phosphate Level at Day 49
timeFrame: Baseline, Day 49
measure: Creatine Phosphokinase (CPK) Level at Baseline
timeFrame: Baseline
measure: Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8
timeFrame: Baseline, Day 8
measure: Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15
timeFrame: Baseline, Day 15
measure: Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25
timeFrame: Baseline, Day 25
measure: Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49
timeFrame: Baseline, Day 49
measure: Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline
timeFrame: Baseline
measure: 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
timeFrame: Baseline, Day 25
measure: 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
timeFrame: Baseline, Day 39
measure: 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
timeFrame: Baseline, Day 49
measure: Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline
timeFrame: Baseline
measure: Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25
timeFrame: Baseline, Day 25
measure: Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39
timeFrame: Baseline, Day 39
measure: Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49
timeFrame: Baseline, Day 49
measure: Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline
timeFrame: Baseline
measure: Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25
timeFrame: Baseline, Day 25
measure: Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39
timeFrame: Baseline, Day 39
measure: Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49
timeFrame: Day 49
measure: Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline
timeFrame: Baseline
measure: Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24
timeFrame: Day 24
measure: Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1
timeFrame: Day 1
measure: Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39
timeFrame: Day 39
measure: Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49
timeFrame: Day 49
Secondary outcomes:
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose
timeFrame: 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
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose
timeFrame: 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
measure: Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023
timeFrame: 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
measure: Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose
timeFrame: 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
measure: Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose
timeFrame: 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
measure: Plasma Decay Half-Life (t1/2) of PF-05231023
timeFrame: 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
measure: Apparent Clearance (CL) of PF-05231023
timeFrame: 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
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research, Inc.
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Elite Research Institute
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates, Inc.
state: Florida
city: South Miami
country: United States
facility: MRA Clinical Research, LLC
state: Florida
city: Lexington
country: United States
facility: Central Kentucky Research Associates, Inc.
state: Kentucky
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Saint Paul
country: United States
facility: Prism Research
state: Minnesota
city: High Point
country: United States
facility: High Point Clinical Trials Center, LLC
state: North Carolina
city: Raleigh
country: United States
facility: Carolina Phase 1 Research
state: North Carolina
city: Raleigh
country: United States
facility: Wake Internal Medicine Consultants
state: North Carolina
city: Cincinnati
country: United States
facility: Medpace Clinical Pharmacology Unit
state: Ohio
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
city: Cincinnati
country: United States
facility: Mercy Hospital Pharmacy
state: Ohio
city: Dallas
country: United States
facility: Covance Clinical Research Unit
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.