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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02435277
• Other study ID #: NS-0100-01E
• Status: Completed
• Phase: Phase 2
• First received: April 13, 2015
• Last updated: December 18, 2017
• Start date: October 2014
• Est. completion date: January 2016

Study information

• Verified date: December 2017
• Source: NuSirt Biopharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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]).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 2016
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 [ß-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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Low Metformin
1100 mg L Leucine in combination with 125 mg of Metformin BID
• Mid Metformin
1100 mg L Leucine in combination with 250mg Metformin BID
• High Metformin
1100 mg of L Leucine in combination with 500 mg Metformin BID
• Metformin
500 mg Metformin BID until day 14 with dose escalation at day 14 to 850 mg Metformin BID

Locations

Country	Name	City	State
United States	River Birch Research Alliance	Blue Ridge	Georgia
United States	Medical Research South	Charleston	South Carolina
United States	Catalina Research Institute	Chino	California
United States	Streling Research Group	Cincinnati	Ohio
United States	Meharry Medical College	Nashville	Tennessee
United States	Vanderbilt University Medical Center, Diabetes, Endocrinology, and Metabolism	Nashville	Tennessee
United States	Palm Beach Research	Palm Beach	Florida
United States	Meridian Research	Savannah	Georgia
United States	Meridien Research	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
NuSirt Biopharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c Levels in Patient Receiving the Various Doses of Leucine and Metformin Combinations	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.	Baseline and 12 weeks
Secondary	Change in Fasting Plasma Glucose	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.	Baseline and 12 weeks