Study of Subcutaneous Doses of HIP2B in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
Verified September 2013 by CureDM
Profil Institute for Clinical Research, Inc.
Information provided by (Responsible Party):
First received: August 5, 2013
Last updated: September 23, 2013
Last verified: September 2013
HIP2B is being developed for the treatment of type 1 and type 2 diabetes mellitus.
The purpose of this study is to investigate the safety and tolerability of repeat doses of HIP2B in subjects with type 2 diabetes mellitus. The study will also assess whether islet β-cell number and function will increase over time in response to repeat HIP2B injections.
Type 2 Diabetes Mellitus
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
||A Randomized, Double-blind, Placebo-controlled Study of the Effect of 49 Days of Treatment With Repeated Subcutaneous Doses of HIP2B to Assess Safety, Tolerability and Measures of Islet β-cell Function in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
Primary Outcome Measures:
- The safety and tolerability of repeat doses of HIP2B in subjects with type 2 diabetes mellitus. [ Time Frame: Adverse Events / vitals are monitored at each study visit between Days -9 and 84. ] [ Designated as safety issue: Yes ]
Safety evaluations will include clinical observation and adverse event (AE) reporting; evaluation of the injection site, physical examination, vital signs; electrocardiograms (ECGs), hematology, chemistry panels (inclusive of expanded markers of liver function), dipstick urinalysis (microscopic evaluation if dipstick positive), amylase, LDH.
Secondary Outcome Measures:
Other Outcome Measures:
- Pre-hepatic insulin secretion rate. [ Time Frame: GGI used for assessments is performed on Day -1, Day 25 and Day 46. ] [ Designated as safety issue: No ]
The pre-hepatic insulin secretion rate will be calculated based on deconvolution of peripheral C-peptide concentrations during GGI using the method described by Hovorka et al.
- Change in β-cell responsiveness. [ Time Frame: GGI measured on Day-1, Day 25 and Day 46. ] [ Designated as safety issue: No ]
Change in β-cell responsiveness will be assessed by comparing the slopes of the change of plasma insulin against glucose before and after treatment.
- PK parameters of HIP2B after single and repetitive dosing. [ Time Frame: PK testing done on Day 1 and Day 46 at pre-dose, 15 and 30min, 1 and 2 hours post dose. ] [ Designated as safety issue: No ]
PK parameters of HIP2B: e.g. Cmax, Tmax, AUC (0.t), AUC(0-∞), CL/F, V/F, t½.
- Pharmacodynamic (PD) effects of repeat doses of HIP2B on measures of glycemic control and β-cell function [ Time Frame: Assessments completed at screening, Days -9, -8, -2, -1, 1, 7, 14, 21, 24, 28, 42, 45, 46, 48, 49, 61, 68, and 84. ] [ Designated as safety issue: No ]
Pharmacodynamic (PD) effects of repeat doses of HIP2B on measures of glycemic control and β-cell function including fasting plasma glucose, fasting C-peptide, fasting proinsulin/insulin ratio and HOMA-B; glycated albumin, HbA1c, and 7-point glucose profiles.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||September 2014 (Final data collection date for primary outcome measure)
Experimental: 600mg HIP2B
Placebo Comparator: Placebo
Experimental: 400mg HIP2B
|Ages Eligible for Study:
||30 Years to 65 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- History of any of the following: type 1 diabetes mellitus, diabetic ketoacidosis, an episode of severe hypoglycemia (defined as a change in mental status requiring assistance) during the prior 30 days
- FPG >260 mg/dL at time of randomization
- Current or chronic use (within past 12 weeks) of insulin, or insulin secretagogues including: sulfonylureas, GLP-1 analogs, DPP-4 inhibitors, meglitinides, α-glucosidase inhibitors, pioglitazone, or rosiglitazone
- Glomerular filtration rate (GFR) <60 as calculated using the Modified Diet in Renal Disease equation at screening
- ALT, AST or total bilirubin > 2 X ULN
- Serum amylase concentration > 1.5XULN or serum lipase concentration >2XULN
- Positive test result for glutamic acid decarboxylase antibodies (GADA).
- The presence of a clinically significant abnormality on resting electrocardiogram (ECG)
- Positive HIV, hepatitis B (HBsAg), or positive hepatitis C (HCV Ab) test at screening
- History of clinically significant renal, hepatic, cardiovascular, neurological, or gastrointestinal disease that could impact patient safety in the investigator's opinion
- Serum triglycerides >500 mg/dL
- Presence or history of cancer within the past 5 years with the exception of adequately treated localized basal cell skin cancer or in situ uterine cervical cancer
- History of weight loss > 5% in the 8 weeks prior to randomization or subject is on a weight loss program and is not in the maintenance phase
- Use of any weight loss medication within 8 weeks of randomization
- Uncontrolled hypertension defined as blood pressure >160/100 mmHg, using an appropriately sized cuff, at rest
- History or evidence of multiple organ autoimmune disorders
- History of thyroid dysfunction other that hypothyroidism treated with stable dose of thyroid hormone and euthyroid at screening
- History or presence of acute or chronic pancreatitis or symptomatic recurrent gallstones
- Has undergone surgery within 6 months of screening or plans to undergo surgery during the study period
- Use of parenterally administered proteins or antibodies within 12 weeks of screening. (Note: Influenza vaccine will be allowed.)
- Prior exposure to any investigational agent or participation in an investigational trial within 30 days prior to Day 1
- Blood loss or blood donation >500 ml in the 2 months prior to screening.
- Use of systemic long-acting corticosteroids within two months or prolonged use (more than one week) of other systemic corticosteroids or inhaled corticosteroids (if daily dosage is >1000 mcg equivalent beclomethasone) within 30 days prior to screening visit.
- Drugs with the potential to affect (either increasing or decreasing) endogenous insulin secretion or insulin sensitivity including corticosteroids (as detailed above), β-adrenergic blockers, beta-adrenergic agonists, quinine, thiazide or thiazide-like diuretics, calcineurin inhibitors, niacin, anti-psychotic or antidepressant drugs, somatostatin analogs, growth hormone, weight-reducing drugs (e.g. orlistat, phentermine and topiramate extended-release, lorcaserin). Stable doses of agents commonly required by subjects with T2DM including angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, statins, fibrates, and aspirin (<100 mg daily) will be permitted at the discretion of the investigator.
- A serious adverse reaction or hypersensitivity to any drug, unless reaction deemed irrelevant to the study by the investigator and sponsor.
- History of alcohol abuse or drug abuse within the previous 12 months. No history of medical or recreational use of marijuana within previous 12 months.
- A history of smoking more than one-half a pack of cigarettes per day within last 12 months
- History of stroke, transient ischemic attack or myocardial infarction within 6 months prior to screening.
- History of New York Heart Association Class II-IV heart failure prior to screening.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01933256
|Profil Institute for Clinical Research, Inc.
|Chula Vista, California, United States, 91911 |
|Contact: Elaine Watkins, D.O. 866-308-7427 email@example.com |
Profil Institute for Clinical Research, Inc.
||Marcus Hompesch, MD
||Profil Institute for Clinical Research, Inc.
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 5, 2013
||September 23, 2013
||United States: Food and Drug Administration
Keywords provided by CureDM:
Type 2 Diabetes Mellitus
islet β cell
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 26, 2014
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Endocrine System Diseases
Physiological Effects of Drugs