Phase 1 N=107 Randomized Quadruple-blind Treatment

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

Diabetes Melliuts, Type 2

Bottom Line

View on ClinicalTrials.gov: NCT01673178 ↗

Enrolled (actual)

107

Serious AEs

3.7%

Results posted

Jan 2015

Primary outcome: Primary: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) — 11; 15; 10; 13 participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Placebo (Other); 25 mg PF-05231023 (Drug); 50 mg PF-05231023 (Drug); 100 mg PF-05231023 (Drug); 150 mg PF-05231023 (Drug)
Age: Adult, Older Adult · 30+ yrs
Sex: All
Sponsor: Pfizer
Primary completion: Aug 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	11; 15; 10; 13; 12; 1	—
PRIMARY Number of Participants With Laboratory Abnormalities	18; 17; 17; 12; 15	—
PRIMARY Number of Participants With Clinically Significant Vital Sign Abnormalities	1; 1; 0; 0; 0; 0	—
PRIMARY Number of Participants With Clinically Significant Electrocardiogram Findings	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Abnormal Physical Examinations	—	—
PRIMARY Thyroid Stimulating Hormone (TSH) Level at Baseline	1.57; 2.14; 1.96; 1.88; 2.06	—
PRIMARY Thyroid Stimulating Hormone (TSH) Level at Day 1	1.96; 2.19; 2.40; 2.26; 4.21	—
PRIMARY Thyroid Stimulating Hormone (TSH) Level at Day 25	2.70; 2.13; 2.43; 2.52; 4.06	—
PRIMARY Thyroid Stimulating Hormone (TSH) Level at Day 39	3.69; 2.08; 2.17; 2.50; 3.10	—
PRIMARY Thyroid Stimulating Hormone (TSH) Level at Day 49	3.42; 1.98; 2.43; 2.55; 3.10	—
PRIMARY Phosphate Level at Baseline	4.1; 3.8; 3.9; 4.0; 4.0	—
PRIMARY Change From Baseline in Phosphate Level at Day 8	-0.2; -0.4; 0.1; 0.0; -0.3	—
PRIMARY Change From Baseline in Phosphate Level at Day 15	-0.2; -0.2; 0.2; -0.1; -0.2	—
PRIMARY Change From Baseline in Phosphate Level at Day 25	-0.1; -0.2; 0.2; 0.1; 0.0	—
PRIMARY Change From Baseline in Phosphate Level at Day 49	-0.40; -0.40; -0.20; -0.30; -0.10	—
PRIMARY Creatine Phosphokinase (CPK) Level at Baseline	73; 94; 94; 103; 108	—
PRIMARY Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8	10; 32; 13; 25; 13	—
PRIMARY Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15	28; 20; 7; 22; 18	—
PRIMARY Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25	-5; -6; -15; -8; -3	—
PRIMARY Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49	21; 40; 27; 43; 10	—
PRIMARY Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	46.3; 41.7; 44.7; 45.0; 44.6; 0.35	—
PRIMARY 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	-0.8; -14.5; -13.4; -17.6; -19.8; 5.2	—
PRIMARY 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	-2.8; -9.8; -6.6; -10.3; -11.0; -7.3	—
PRIMARY 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	-3.0; -9.4; -1.3; -4.6; -7.4; 1.5	—
PRIMARY Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	18.8; 19.2; 18.5; 20.2; 19.9; 13.0	—
PRIMARY Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	-2.4; -12.2; -6.4; -7.1; -4.8; -4.3	—
PRIMARY Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	-1.8; -10.7; -11.6; -14.7; -13.4; -5.0	—
PRIMARY Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	-4.5; -10.7; -5.1; -11.0; -4.8; -3.8	—
PRIMARY Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline	2.97; 2.72; 3.10; 2.78; 3.08	—
PRIMARY Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25	1.3; -1.7; 1.9; -0.4; -1.4	—
PRIMARY Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39	0.5; -0.4; 0.2; -2.9; 3.7	—
PRIMARY Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49	-2.4; 3.1; -0.8; -0.1; -1.1	—
PRIMARY Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	296.4; 202.1; 224.3; 205.3; 207.4; 922.1	—
PRIMARY Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	-29.3; -9.1; 38.0; 8.2; 5.1; 18.8	—
PRIMARY Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1	0; 0; 0; 0; NA; NA	—
PRIMARY Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39	0; 0; 0; 1; NA; NA	—
PRIMARY Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	0; 1; 0; 1; NA; 1	—
SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	108100; 206200; 376600; 475600; 376100; 693400	—
SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	0.5; 0.5; 0.5; 0.5; 1.0; 1.0	—
SECONDARY Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	7983; 15250; 32980; 48320; 8881; 16800	—
SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	76520; 136200; 301200; 424700; 467700; 855500	—
SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	0.55; 0.53; 0.79; 1.00; 1.00; 1.00	—
SECONDARY Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	7697; 14450; 29610; 42260; 9981; 16900	—
SECONDARY Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	0.70; 0.65; 0.79; 0.90; 1.24; 1.28	—
SECONDARY Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	0.93; 0.96; 0.89; 0.89; 1.13; 1.04	—
SECONDARY Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	0.0001000; 0.0001000; 0.0001000; 0.0001866; 768.3; 1213	—
SECONDARY Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	455.8; 810.7; 1793; 2529; 2783; 5091	—
SECONDARY Plasma Decay Half-Life (t1/2) of PF-05231023	7.6; 7.4; 7.4; 8.6; 121.6; 119.3	—
SECONDARY Apparent Clearance (CL) of PF-05231023	0.33; 0.37; 0.33; 0.35; 0.05; 0.06	—

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01673178). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.