Safety and Tolerability of Ascending Intravenous Doses of PF-05231023 In Adult Subjects With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Phase 1, Placebo-Controlled Randomized Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Ascending Intravenous Doses Of PF-05231023 In Adult Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01396187
• Other study ID #: B2901002
• Status: Completed
• Phase: Phase 1
• First received: July 6, 2011
• Last updated: December 30, 2014
• Start date: July 2011
• Est. completion date: May 2012

Study information

• Verified date: December 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a trial in subjects with Type 2 diabetes mellitus to study the safety, tolerability and pharmacokinetics of multiple ascending doses of PF-05231023.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male subjects and female subjects of non-childbearing potential between the ages of 30 and 70 years, inclusive, with a historical diagnosis of type 2 diabetes mellitus, diagnosed according to the American Diabetes Association guidelines. Subjects who have other conditions but are well controlled by either diet or medications may be included as well (for example, a subject with high cholesterol level on appropriate treatment is eligible).

• Body Mass Index (BMI) of 25 to 35.5 kg/m2, and a total body weight >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 untreated, asymptomatic, seasonal allergies at time of dosing).

• Diagnosis of Type 1 diabetes mellitus.

• Evidence of diabetic complications with significant end organ damage

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• PF-05231023
5 mg IV twice a week for 4 weeks
• PF-05231023
25 mg IV twice a week for 4 weeks
• PF-05231023
100 mg IV twice a week for 4 weeks
• PF-05231023
200 mg IV twice a week for 4 weeks

Other:
• Placebo
0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), twice a week IV for 4 weeks

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Chula Vista	California
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Overland Park	Kansas
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	South Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Abnormal Physical Examination Findings	Physical examination included assessment of height, weight, blood pressure, pulse rate and body temperature. Criteria for abnormal physical findings was based on investigator's discretion and were reported as adverse event (AE), as planned.	Baseline up to Day 42	Yes
Primary	Number of Participants With Treatment-Emergent Adverse Events (AEs) or 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 are events between first dose of study drug and up to Day 77 which were absent before treatment or that worsened relative to pretreatment state.	Baseline up to Day 77	Yes
Primary	Number of Participants With Abnormal Laboratory Values	Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (RBCs)(less than [<] 0.8*lower limit of normal[LLN]); leucocytes (<0.6/greater than [>]1.5*upper limit of normal [ULN]); platelets (<0.5*LLN>	Baseline up to Day 42	Yes
Primary	Number of Participants With Vital Signs Abnormalities	Criteria for vital signs abnormalities: supine systolic blood pressure (SBP) <90 millimeter of mercury (mm Hg), supine diastolic BP (DBP) <50 mm Hg, supine pulse rate <40 beats per minute (bpm), > 120 bpm. Maximum increase or decrease from baseline in supine SBP >=30 mm Hg and maximum increase or decrease from baseline in supine DBP >=20 mm Hg.	Baseline up to Day 77	Yes
Primary	Number of Participants With Electrocardiogram (ECG) Abnormalities	Criteria for potential clinical concern in ECG parameters: maximum PR interval of greater than or equal to (>=) 300 milliseconds (msec), maximum QRS interval >=140 msec, maximum QTCF interval (Fridericia's Correction) of 450 to <480 msec, 480 to <500 msec and >=500 msec, maximum increase of >=25 percent (%) for baseline value of >200 msec and >=50% for baseline value of less than or equal to (<=) 200 msec for PR interval, maximum increase from baseline of >=50% for QRS interval, maximum increase from baseline of >=30 msec to <60 msec and maximum increase from baseline of >60 msec in QTCF interval (Fridericia's Correction).	Baseline up to Day 77	Yes
Primary	Number of Participants With Blood Glucose Abnormalities	Criteria for blood glucose abnormality: Blood glucose levels <0.6* LLN or >1.5* ULN.	Baseline up to Day 32	Yes
Secondary	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	Participants who received PF-05231023 with C-terminal and N-terminal AUCtau were reported.	0 hour (pre-dose) on Day 1, 4; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1; Day 2, 3	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	Participants who received PF-05231023 with C-terminal and N-terminal Tmax were reported.	0 hour (pre-dose) on Day 1, 4; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1; Day 2, 3	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	Participants who received PF 05231023 with C-terminal and N-terminal Cmax were reported.	0 hour (pre-dose) on Day 1, 4; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1; Day 2, 3	No
Secondary	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 at Steady State	Participants who received PF-05231023 with C-terminal and N-terminal AUCtau at steady state were reported.	0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05231023 at Steady State	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) at steady state. Participants who received PF-05231023 with C-terminal and N-terminal AUClast at steady state were reported.	0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 at Steady State	Participants who received PF-05231023 with C-terminal and N-terminal Tmax at steady state were reported.	0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 at Steady State	Participants who received PF 05231023 with C-terminal and N-terminal Cmax at steady state were reported.	0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29	No
Secondary	Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval of PF-05231023 (Rac)	Rac was obtained from AUCtau at steady state (Day 25) divided by AUCtau after single dose (Day 1). AUCtau was the area under the concentration-time profile from time zero to end of dosing interval, where tau = 72 hours for Day 1 and tau = 96 hours for Day 25. Participants who received PF-05231023 with C-terminal and N-terminal Rac at steady state were reported.	0 hour (pre-dose) on Day 1, 4, 25; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1, 25; Day 2, 3, 26, 29	No
Secondary	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF- 05231023	Accumulation ratio based on maximum plasma concentration (Cmax) was calculated as: Rac,Cmax = Cmax at steady state (Day 25) divided by Cmax at first dose (Day 1). Participants who received PF-05231023 with C-terminal and N-terminal Rac,Cmax at steady state were reported.	0 hour (pre-dose) on Day 1, 4, 25; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1, 25; Day 2, 3, 26, 29	No
Secondary	Plasma Terminal Half-Life (t1/2) of PF-05231023 at Steady State	Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half at the terminal phase. Participants who received PF-05231023 with C-terminal and N-terminal t1/2 at steady state were reported.	0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29	No
Secondary	Apparent Clearance (CL) of PF-05231023 at Steady State	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Participants who received PF-05231023 with C-terminal and N-terminal CL at steady state were reported.	0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29	No
Secondary	Volume of Distribution of PF-05231023 at Steady State (Vss)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state. PF-05231023 with C-terminal and N-terminal Vss at steady state were reported.	0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29	No
Secondary	Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 at Steady State	Participants who received PF 05231023 with C-terminal and N-terminal Cmax at steady state were reported.	0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29	No
Secondary	Average Plasma Concentration (Cav) of PF-05231023 at Steady State	Participants who received PF-05231023 with C-terminal and N-terminal Cmax at steady state were reported.	0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29	No

External Links

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