Clinical trial NCT01933256: Study of Subcutaneous Doses of HIP2B in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes Mellitus
HIP2B
Placebo
islet β cell
Lead sponsor: CureDM
Sponsor class: INDUSTRY
Collaborators: name: Profil Institute for Clinical Research, Inc.
First posted: 2013-09-02
Enrollment: 32
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Adults aged 30 to 65 years, inclusive
* Males and females
* Diagnosis of type 2 diabetes mellitus prior to screening meeting the following criteria:

  1. Body mass index \<45 kg/m2
  2. HbA1c value of \> 6.5 to \<9.5%
  3. C-peptide ≥1.0 ng/mL
  4. On a stable dose of metformin for 12 weeks
* Ability to provide written informed consent and be willing to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion Criteria:

* 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.

Primary outcomes:
measure: The safety and tolerability of repeat doses of HIP2B in subjects with type 2 diabetes mellitus.
timeFrame: Adverse Events / vitals are monitored at each study visit between Days -9 and 84.
Secondary outcomes:
measure: Glucose-stimulated insulin secretion.
timeFrame: IVGTT performed on Day -8 and Day 49. GGI performed on Day -1, Day 25 and Day 46.
Other outcomes:
measure: Pre-hepatic insulin secretion rate.
timeFrame: GGI used for assessments is performed on Day -1, Day 25 and Day 46.
measure: Change in β-cell responsiveness.
timeFrame: GGI measured on Day-1, Day 25 and Day 46.
measure: PK parameters of HIP2B after single and repetitive dosing.
timeFrame: PK testing done on Day 1 and Day 46 at pre-dose, 15 and 30min, 1 and 2 hours post dose.
measure: Pharmacodynamic (PD) effects of repeat doses of HIP2B on measures of glycemic control and β-cell function
timeFrame: Assessments completed at screening, Days -9, -8, -2, -1, 1, 7, 14, 21, 24, 28, 42, 45, 46, 48, 49, 61, 68, and 84.
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research, Inc.
state: California
Study officials:
affiliation: Profil Institute for Clinical Research, Inc.
name: Marcus Hompesch, MD
role: PRINCIPAL_INVESTIGATOR
References: