An Extension Protocol to Evaluate Dose Comparisons of Leucine-Metformin Combinations in Type 2 Diabetic Patients

• ClinicalTrials.gov Identifier: NCT02435277
• Recruitment Status: Completed
• First Posted: May 6, 2015
• Results First Posted: December 18, 2017
• Last Update Posted: January 17, 2018
• Sponsor: NuSirt Biopharma
• Information provided by (Responsible Party): NuSirt Biopharma

Study Description

Brief Summary:

Study NS-0100-01E is an extension of Study NS-01-0100 designed to assess safety and longer term effect (i.e., additional 8 weeks) of various fixed-dose leucine and metformin combinations (NS-0100) versus standard metformin monotherapy on glycemic control in subjects with type 2 diabetes using HbA1c as the primary endpoint.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: Low Metformin; Drug: Mid Metformin; Drug: High Metformin; Drug: Metformin	Phase 2

Detailed Description:

This is a randomized, 8-week, extension of Study NS-0100-01, to evaluate the effect of various fixed-dose (FDC) combinations of leucine and metformin compared to standard metformin monotherapy on glycemic control.

Subjects meeting all inclusion criteria and no exclusion criteria for the extension study, including completion of the 4-week treatment period of Study NS-0100-01 [Day 28/Visit 7]), will be eligible to enroll into the extension. During participation in the extension, subjects will continue to receive their assigned treatment based upon the randomization that occurred on Day 1 (Visit 4) of Study NS-0100-0. The study will include a total of 3 visits: Visit 1E (Day 28/Visit 7 of Study NS-0100-01), Visit 2E (Day 56/Week 8), and Visit 3E (Day 84/Week 12). Key assessments at Visit 2E and Visit 3E include HbA1c, fasting plasma glucose, and plasma insulin. In addition, 3-hour standardized meal tests will be performed on Day 28 (as part of the Study Termination [Visit 7] procedures of Study NS-0100-01 prior to enrolling into the extension) and at Study Termination for the extension (Visit 3E [Day 84/Week 12]).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Extension of Protocol NS-0100-01 to Evaluate the Safety and Effect of Various Fixed-Dose Leucine and Metformin Combinations (NS-0100) Versus Standard Metformin Mono-therapy on Glycemic Control in Subjects With Type 2 Diabetes
• Study Start Date: October 2014
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: January 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low Metformin; 3 capsules BID with each capsule containing 366.7 mg L-Leucine and 41.7 mg of metformin	Drug: Low Metformin; 1100 mg L Leucine in combination with 125 mg of Metformin BID; Other Name: Metformin, L-Leucince, Leucine
Experimental: Mid Metformin; 3 capsules BID with each capsule containing 366.7 mg L-Leucine and 83.3 mg of metformin	Drug: Mid Metformin; 1100 mg L Leucine in combination with 250mg Metformin BID; Other Name: Metformin, Leucine, L-Leucine
Experimental: High Metformin; 3 capsules BID with each capsule containing 366.7 mg L-Leucine and 166.7 mg of metformin	Drug: High Metformin; 1100 mg of L Leucine in combination with 500 mg Metformin BID; Other Name: Metformin, Leucine, L-Leucine
Active Comparator: Metformin Monotherapy; 3 Capsules BID each containing 283.3 mg of metformin BID (1,700 mg/Day) at Day 14.	Drug: Metformin; 500 mg Metformin BID until day 14 with dose escalation at day 14 to 850 mg Metformin BID; Other Name: Metformin, Leucine, L-Leucine

Outcome Measures

Primary Outcome Measures :

1. Change in HbA1c Levels in Patient Receiving the Various Doses of Leucine and Metformin Combinations [ Time Frame: Baseline and 12 weeks ]
   Change in HbA1c from Baseline (Day 1/Visit 1) of Study NS-0100-01 to Week 12 (Day 84/Visit 3E) in subjects receiving various fixed-dose combinations of leucine and metformin compared to standard metformin monotherapy.

Secondary Outcome Measures :

1. Change in Fasting Plasma Glucose [ Time Frame: Baseline and 12 weeks ]
   Change in fasting plasma glucose from Baseline (Day 1/Visit 1) of Study NS-0100-01 to Week 12 (Day 84/Visit 3E). Based on the pre-specified mixed model inferential statistical analysis, there was an apparent dose-dependent relationship for the mean decrease from baseline in fasting plasma glucose for the fixed dose leucine amd metformin combination treatments A, B and C.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Has completed Study NS-0100-01, including all procedures required at Study Termination (Day 28/Visit 7) without major protocol deviations

2. Is male, or female and, if female, meets all of the following criteria:

   • Not breastfeeding
   • Post-menopausal or negative pregnancy test result (human chorionic gonadotropin, beta subunit [β-hCG]) at Screening (Visit 1) (not required for hysterectomized females)
   • If of childbearing potential (including perimenopausal women who have had a menstrual period within one year) and sexually active, must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods [male condom with spermicide, with or without cervical cap or diaphragm], implants, injectables, oral contraceptives [must have been using for at least the last 3 months], some intrauterine contraceptive devices, tubal ligation, or a vasectomized partner) during the entire duration of the study.
3. Is able to read, understand, and sign the informed consent forms (ICF) and if applicable, an authorization to use and disclose protected health information form (consistent with health insurance portability and accountability act of 1996 [HIPAA] legislation), communicate with the investigator, and understand and comply with protocol requirements.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study.

1. Is undesirable as a study participant as judged by the investigator (e.g., exhibited poor compliance during Study NS-0100-01)

2. Is expected to require treatment, or if currently on a stable dose, changes to their regimen of the following medications:

   • Lipid-lowering agents
   • Anti-hypertensive medications
   • Thyroid replacement therapy
   • Non-steroidal anti-inflammatory agents

3. Is expected to require or undergo treatment with any of the following medications:

   • Antidiabetes medications (with the exception of study medication [i.e., metformin])
   • Oral or parenteral steroids.

Contacts and Locations

Locations

United States, California

Catalina Research Institute

Chino, California, United States, 91710

United States, Florida

Palm Beach Research

Palm Beach, Florida, United States, 33409

Meridien Research

Tampa, Florida, United States, 33606

United States, Georgia

River Birch Research Alliance

Blue Ridge, Georgia, United States, 3051313

Meridian Research

Savannah, Georgia, United States, 31406

United States, Ohio

Streling Research Group

Cincinnati, Ohio, United States, 45219

United States, South Carolina

Medical Research South

Charleston, South Carolina, United States, 29407

United States, Tennessee

Meharry Medical College

Nashville, Tennessee, United States, 37208

Vanderbilt University Medical Center, Diabetes, Endocrinology, and Metabolism

Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

NuSirt Biopharma

Investigators

• Study Chair: Orville Kolterman, MD; Pharmapace

More Information

• Responsible Party: NuSirt Biopharma
• ClinicalTrials.gov Identifier: NCT02435277
• Other Study ID Numbers: NS-0100-01E
• First Posted: May 6, 2015
• Results First Posted: December 18, 2017
• Last Update Posted: January 17, 2018
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by NuSirt Biopharma:

Diabetes

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs