Study of Subcutaneous Doses of HIP2B in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
This study has been completed.
Profil Institute for Clinical Research, Inc.
Information provided by (Responsible Party):
First received: August 5, 2013
Last updated: November 14, 2016
Last verified: November 2016
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.
| Study Start Date:
| Study Completion Date:
| 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 (Adult)
|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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01933256
|Profil Institute for Clinical Research, Inc.
|Chula Vista, California, United States, 91911 |
Profil Institute for Clinical Research, Inc.
||Marcus Hompesch, MD
||Profil Institute for Clinical Research, Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 5, 2013
||November 14, 2016
||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 December 05, 2016
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Endocrine System Diseases
Physiological Effects of Drugs