Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes
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.
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 \[Day 84/Week 12\]).
Interventions
DRUGLow Metformin
1100 mg L Leucine in combination with 125 mg of Metformin BID
DRUGMid Metformin
1100 mg L Leucine in combination with 250mg Metformin BID
DRUGHigh Metformin
1100 mg of L Leucine in combination with 500 mg Metformin BID
DRUGMetformin
500 mg Metformin BID until day 14 with dose escalation at day 14 to 850 mg Metformin BID
Sponsors
NuSirt Biopharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c Levels in Patient Receiving the Various Doses of Leucine and Metformin Combinations | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose | 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. |
Countries
United States
Participant flow
Recruitment details
Study NS-0100-01E was a randomized, double-blind 8-week extension of Study NS-0100-01 to evaluate the effect of various fixed-dose combinations of leucine and metformin compared to standard metformin monotherapy on glycemic control.
Pre-assignment details
Subjects meeting all inclusion criteria and no exclusion criteria for the NS-001-01-E, including completion of the 4-week treatment period of Study NS-0100-01 (Day 28/Visit 7), were eligible to enroll into the NS-001-01-E.
Participants by arm
| Arm | Count |
|---|---|
| FDC 125 Leucine 1100mg +Metformin 125mg | 12 |
| FDC 250 Leucine 1100mg +Metformin 250mg | 16 |
| FDC 500 Leucine 1100mg +Metformin 500mg | 11 |
| Control 850mg Metformin | 11 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | FDC 125 | FDC 250 | FDC 500 | Control | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 13 Participants | 8 Participants | 9 Participants | 40 Participants |
| Age, Continuous | 51.8 years STANDARD_DEVIATION 10.81 | 56.1 years STANDARD_DEVIATION 8.24 | 59.8 years STANDARD_DEVIATION 9.01 | 60.5 years STANDARD_DEVIATION 8.77 | 56.9 years STANDARD_DEVIATION 9.52 |
| Body Mass Index (BMI) | 33.298 (kg/m^2 STANDARD_DEVIATION 4.4952 | 31.647 (kg/m^2 STANDARD_DEVIATION 6.3242 | 28.627 (kg/m^2 STANDARD_DEVIATION 4.5195 | 32.677 (kg/m^2 STANDARD_DEVIATION 5.3808 | 31.606 (kg/m^2 STANDARD_DEVIATION 5.4597 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 8 Participants | 2 Participants | 4 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 9 Participants | 7 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fasting Plasma Glucose | 173.5 mg/dL STANDARD_DEVIATION 31.13 | 150.5 mg/dL STANDARD_DEVIATION 26.78 | 179.2 mg/dL STANDARD_DEVIATION 36.04 | 177.1 mg/dL STANDARD_DEVIATION 53.67 | 168.2 mg/dL STANDARD_DEVIATION 38 |
| Haemoglobin A1c (HbA1c) | 7.56 % STANDARD_DEVIATION 0.644 | 7.83 % STANDARD_DEVIATION 0.769 | 7.84 % STANDARD_DEVIATION 0.545 | 7.92 % STANDARD_DEVIATION 0.645 | 7.79 % STANDARD_DEVIATION 0.661 |
| Previous Metformin experience No Previous Experience | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 8 Participants |
| Previous Metformin experience Prior taken metformin: Had abdominal side effects | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 7 Participants |
| Previous Metformin experience Prior taken metformin: No Abdominal side effects | 9 Participants | 11 Participants | 7 Participants | 8 Participants | 35 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 5 Participants | 4 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 13 Participants | 6 Participants | 7 Participants | 36 Participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 6 Participants | 7 Participants | 29 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 5 Participants | 4 Participants | 21 Participants |
| Weight | 93.343 kg STANDARD_DEVIATION 19.0179 | 91.314 kg STANDARD_DEVIATION 18.7664 | 87.497 kg STANDARD_DEVIATION 21.2259 | 90.500 kg STANDARD_DEVIATION 18.4163 | 90.782 kg STANDARD_DEVIATION 18.823 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 16 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 2 / 12 | 2 / 16 | 2 / 11 | 1 / 11 |
| serious Total, serious adverse events | 0 / 12 | 1 / 16 | 0 / 11 | 0 / 11 |
Outcome results
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.
Time frame: Baseline and 12 weeks
Population: Mixed Model Inferential Statistical Analysis of HbA1c change from day 1-day 84 Evaluable Population (n=43)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC 125 | Change in HbA1c Levels in Patient Receiving the Various Doses of Leucine and Metformin Combinations | 0.10 percent HbA1c | Standard Deviation 0.756 |
| FDC 250 | Change in HbA1c Levels in Patient Receiving the Various Doses of Leucine and Metformin Combinations | -0.12 percent HbA1c | Standard Deviation 0.987 |
| FDC 500 | Change in HbA1c Levels in Patient Receiving the Various Doses of Leucine and Metformin Combinations | -0.05 percent HbA1c | Standard Deviation 0.807 |
| Control | Change in HbA1c Levels in Patient Receiving the Various Doses of Leucine and Metformin Combinations | -0.83 percent HbA1c | Standard Deviation 0.627 |
Comparison: Mixed Model Inferential Statistical Analysis of HbA1c change from day 1-day 84 Evaluable Population (n=43)p-value: 0.0475ANCOVA
p-value: 0.0912ANCOVA
p-value: 0.0458ANCOVA
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.
Time frame: Baseline and 12 weeks
Population: Mixed Model Inferential Statistical Analysis of Fasting Plasma Glucose change from day 1-day 84 in Evaluable Population (n=43)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC 125 | Change in Fasting Plasma Glucose | -15.8 mg/dL | Standard Deviation 22.29 |
| FDC 250 | Change in Fasting Plasma Glucose | 11.2 mg/dL | Standard Deviation 22.37 |
| FDC 500 | Change in Fasting Plasma Glucose | -4.3 mg/dL | Standard Deviation 39.91 |
| Control | Change in Fasting Plasma Glucose | -36.3 mg/dL | Standard Deviation 45.47 |
Comparison: Mixed Model Inferential Statistical Analysis of Fssting Plasma Glucose change from day 1-day 84 in Evaluable Population (n=43)p-value: 0.26ANCOVA
p-value: 0.0083ANCOVA
p-value: 0.0317ANCOVA