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

NCT01673178 | Completed Phase 1 Results

• 1 other identifier: B2901011
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 17

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

Conditions

Diabetes Melliuts, Type 2

Keywords

Type 2 diabetes; safety; multiple dose; intravenous

Outcome Measures

Primary Outcomes (37)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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.

  Baseline up to 28 days after last dose

• Number of Participants With Laboratory Abnormalities

  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 \[HPF\]).

  Baseline up to Day 49

• Number of Participants With Clinically Significant Vital Sign Abnormalities

  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.

  Baseline up to Day 49

• Number of Participants With Clinically Significant Electrocardiogram Findings

  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.

  Baseline up to Day 49

• Number of Participants With Abnormal Physical Examinations

  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.

  Baseline up to Day 49

• Thyroid Stimulating Hormone (TSH) Level at Baseline

  Results are reported in micro international units per milliliter (mcIU/mL).

  Baseline

• Thyroid Stimulating Hormone (TSH) Level at Day 1

  Day 1

• Thyroid Stimulating Hormone (TSH) Level at Day 25

  Day 25

• Thyroid Stimulating Hormone (TSH) Level at Day 39

  Day 39

• Thyroid Stimulating Hormone (TSH) Level at Day 49

  Day 49

• Phosphate Level at Baseline

  Baseline

• Change From Baseline in Phosphate Level at Day 8

  Baseline, Day 8

• Change From Baseline in Phosphate Level at Day 15

  Baseline, Day 15

• Change From Baseline in Phosphate Level at Day 25

  Baseline, Day 25

• Change From Baseline in Phosphate Level at Day 49

  Baseline, Day 49

• Creatine Phosphokinase (CPK) Level at Baseline

  Baseline

• Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8

  Baseline, Day 8

• Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15

  Baseline, Day 15

• Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25

  Baseline, Day 25

• Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49

  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

  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

  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

  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

  Baseline, Day 49

• Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline

  Baseline

• Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25

  Baseline, Day 25

• Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39

  Baseline, Day 39

• Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49

  Baseline, Day 49

• Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline

  Baseline

• Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25

  Baseline, Day 25

• Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39

  Baseline, Day 39

• Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49

  Day 49

• Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline

  Baseline

• Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24

  Day 24

• Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at 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.

  Day 1

• Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at 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.

  Day 39

• Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49

  Day 49

Secondary Outcomes (12)

• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose

  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

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose

  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

• Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose

  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

• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose

  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

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose

  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

Study Arms (5)

Placebo Arm

PLACEBO COMPARATOR

Other: Placebo

25 mg

EXPERIMENTAL

Drug: 25 mg PF-05231023

50 mg

EXPERIMENTAL

Drug: 50 mg PF-05231023

100 mg

EXPERIMENTAL

Drug: 100 mg PF-05231023

150 mg

EXPERIMENTAL

Drug: 150 mg PF-05231023

Interventions

Placebo OTHER

0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), once a week for 4 weeks

Placebo Arm

25 mg PF-05231023 DRUG

25 mg IV once a week for 4 weeks

25 mg

50 mg PF-05231023 DRUG

50 mg IV once a week for 4 weeks

50 mg

100 mg PF-05231023 DRUG

100 mg IV once a week for 4 weeks

100 mg

150 mg PF-05231023 DRUG

150 mg IV once a week for 4 weeks

150 mg

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (17)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Profil Institute for Clinical Research, Inc.

Chula Vista, California, 91911, United States

Location

Diablo Clinical Research, Inc.

Walnut Creek, California, 94598, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

Elite Research Institute

Miami, Florida, 33169, United States

Location

Miami Research Associates, Inc.

South Miami, Florida, 33143, United States

Location

MRA Clinical Research, LLC

South Miami, Florida, 33143, United States

Location

Central Kentucky Research Associates, Inc.

Lexington, Kentucky, 40509, United States

Location

L-MARC Research Center

Louisville, Kentucky, 40213, United States

Location

Prism Research

Saint Paul, Minnesota, 55114, United States

Location

High Point Clinical Trials Center, LLC

High Point, North Carolina, 27265, United States

Location

Carolina Phase 1 Research

Raleigh, North Carolina, 27612, United States

Location

Wake Internal Medicine Consultants

Raleigh, North Carolina, 27612, United States

Location

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45227, United States

Location

Community Research

Cincinnati, Ohio, 45255, United States

Location

Mercy Hospital Pharmacy

Cincinnati, Ohio, 45255, United States

Location

Covance Clinical Research Unit

Dallas, Texas, 75247, United States

Location

Related Publications (1)

• 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.

  PMID: 28573777 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

PF-05231023

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2012
• First Posted: August 27, 2012
• Study Start: October 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: September 1, 2013
• Last Updated: February 16, 2015
• Results First Posted: January 14, 2015

Record last verified: 2015-01

Locations

US (17)