Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, Type 2 Diabetes
Brief summary
The goal of this study is to demonstrate that leucine in combination with a low does of metformin can serve as an adjunct to diet and exercise to improve blood glucose levels in type 2 diabetic subjects. This study will compare three doses of a leucine-metformin combination to the standard metformin dose in controlling blood glucose levels in type 2 diabetic patients.
Detailed description
This is a randomized, 4-week, active-controlled, double-blind study to evaluate the effect of various fixed-dose combinations of leucine and metformin compared to standard metformin monotherapy on glycemic control. In this study, standard metformin therapy will be defined as 1000 g/day for Day 1 to Day 14 and then escalated to 1700 g/day for Day 15 to Day 28. Subjects meeting all inclusion criteria and no exclusion criteria will be randomized to one of four treatment arms. The primary objective of the study is to evaluate the change in fasting plasma glucose from Baseline (Day 1) to Week 4 (Day 28) in subjects receiving various fixed-dose combinations of leucine and metformin compared to standard metformin monotherapy. Secondary objectives will also assess changes in baseline-corrected plasma glucose and insulin area under the concentration curves from baseline to day 28 and changes in insulin secretory rates as assessed during a 3-hour meal tolerance test. Finally the effects of gastrointestinal symptoms will be assessed by subject questionnaires. The study will include a total of 3 periods: screening or washout of current diabetic monotherapy, a pre-treatment period to ensure subjects will be compliant, and a treatment period of 4 weeks, with the first dosing of medication on day 1 of the study. Each day blood glucose readings will be measured and recorded by patients. Three-hour standardized meal tests will be performed at Baseline (Day 1) and at Study Termination (Day 28). In addition, two, 7-day continuous glucose assessments will be conducted, as well as two seven point glucose profiles. Patients will also be asked about any gastrointestinal side effects they experience.
Interventions
DRUGLow Metformin
1100 mg L Leucine in combination with 125 mg of Metformin BID
DRUGMetformin
500 mg metformin BID until day 14 with dose escalation at day 14 to 850 mg metformin BID
DRUGMid Metformin
1100 mg of Leucine in combination with 250 mg Metformin BID
DRUGHigh Metformin
1100 mg of Leucine in combination with 500 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
* Over age 18 at study entry. * Male, or female, 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 and sexually active, must practice and be willing to continue to practice appropriate birth control * Is diagnosed with type 2 diabetes mellitus and either not adequately controlled by: diet and exercise alone or diet and exercise plus a single, first line treatment for type 2 diabetes. * If treated with an oral anti-diabetes agent, be willing and able to withdraw from therapy for 4 weeks after the screening visit and prior to initiating study mediation at Baseline (Day 1/Visit 4). * Be willing to avoid acetaminophen use for intervals up to 10 days as required for study procedures (see Section 4.6) * Has a fasting plasma glucose ≥126 mg/dL to ≤220 mg/dL at Screening * Has an HbA1c ≥7% to ≤8.5% at Screening * Has a BMI ≤40 kg/m2 * Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either normal or abnormal but consistent with type 2 diabetes mellitus. * 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
* Clinically significant renal dysfunction * If using any of the following medications, has not been on a stable treatment regimen for a minimum of 4 weeks prior to screening: Lipid-lowering agents Anti-hypertensive medications Thyroid replacement therapy Non-steroidal anti-inflammatory agents * Unable to perform self-blood glucose monitoring employing a glucose meter. * History of active cardio- or cerebro-vascular disease with an event within the previous 6 months * Gastrointestinal disorders * Endocrine disorders other than type 2 diabetes * Chronic infection * Hepatic disease * Neurological or psychiatric diseases * History of other psychiatric disorders * Has been treated (within the last month), is currently treated, or is expected to require or undergo treatment with; any anti-diabetes medications (other than as allowed by the inclusion criteria), oral or parenteral steroids. * Participation in a weight loss program within the past 3 months. * Weight change by more than 10 pounds during the past month. * History of alcohol or substance abuse in the past 3 months or a positive screen for alcohol or drugs of abuse at screening. * Has received any investigational drug within 3 months of Screening. * Has donated blood within 3 months before Screening or is planning to donate blood during the study. * Has known allergies or hypersensitivity to metformin or leucine * Is employed, contracted or has an immediate family member directly affiliated with NuSirt Biopharma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 28 in Absolute Plasma Glucose Area Under the Curve (AUC) 0-3hr | 0, 15min, 30min, 45min, 1hr, 1.5hrs, 2hrs, 2.5hrs and 3 hrs | The primary endpoint for NS 0100 01 was the absolute plasma glucose AUC (0-3 hr) change from Day 1 to Day 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 28 in Incremental Plasma Glucose Area Under the Curve (AUC) | Baseline, Day 28 | The baseline incremental (baseline-subtracted) glucose AUC0-3h was evaluated for treatment differences at baseline. |
| Change in Fasting Plasma Glucose | Baseline, Day 28 | Change in fasting plasma glucose for the fixed dose leucine and metformin combination treatments A, B and C was evaluated. |
| Change in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | Baseline, Day 28 | Effect on insulin sensitivity across fixed-dose leucine and metformin combination treatments or the standard metformin reference treatment. |
| Change in Hemoglobin A1c (HbA1c) | Baseline, Day 28 | Changes in HbA1c which is a marker of long-term glucose control was assessed. |
| Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr | Baseline,Day 28 | Change in meal tolerance test insulin area under the curve (0-2 hr) from Day 1 to Day 28 for fixed-dose leucine and metformin combination treatments. |
| Change From Baseline to Day 28 in Fasting Plasma Insulin Concentration | Baseline, Day 28 | Effect on fasting plasma insulin concentrations across fixed-dose leucine and metformin combination treatments or the standard metformin reference treatment was evaluated. |
| Change In 7-Point Glucose Profiles | Baseline, Day 7, Day 21, Day 28 | The meal induced glucose change in pre-meal and post-meal glucose were measured 7 times during the day. Subjects self-monitored blood glucose (preprandial and postprandial) concentrations at least 7 times, including before and 1 to 2 hours after breakfast, lunch, dinner, and snacks). For each study day, the pre-meal values from the 7 point test for each subject were averaged to generate a single pre-meal glucose value. Similarly, for each study day the post-meal values from the 7-point test for each subject were averaged to generate a single post-meal glucose value. The average change from baseline (i.e., \[(Mean Pre/Post-meal value at Day 28 - Mean Pre/Post-meal value at Baseline) + (Mean Pre/Post-meal value at Day 21- Mean Pre/Post-meal value at Baseline) + (Mean Pre/Post-meal value at Day 7- Mean Pre/Post-meal value at Baseline)\]/ 3) over multiple time points listed in Time Frame. The mean pre-meal and post-meal values for baseline, day7, day 21 and day28 were used for comparison. |
Countries
United States
Participant flow
Recruitment details
Subjects meeting all inclusion criteria and no exclusion criteria were randomized to one of four treatment arms in the ratio of 1:1:1:1 (A:B:C:D). The randomization was stratified by fasting plasma glucose (≥126 mg/dL to \<200 mg/dL, and ≥200 mg/dL to ≤220 mg/dL), as well as metformin experience. Yes/No history of abdominal side effects.
Participants by arm
| Arm | Count |
|---|---|
| FDC125 Leucine 1100mg +Metformin 125mg | 24 |
| FDC250 Leucine 1100mg +Metformin 250mg | 25 |
| FDC500 Leucine 1100mg +Metformin 500mg | 24 |
| Control Day 1-14: 500mg, Day 15-28: 850mg | 23 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 1 | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 |
| Overall Study | Treatment discontinuation | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | FDC125 | FDC250 | FDC500 | Control | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 9.87 | 55.1 years STANDARD_DEVIATION 8.3 | 56.1 years STANDARD_DEVIATION 10.08 | 59.3 years STANDARD_DEVIATION 9.64 | 56.0 years STANDARD_DEVIATION 9.56 |
| Age, Customized <65 years | 19 Participants | 21 Participants | 18 Participants | 17 Participants | 75 Participants |
| Age, Customized ≥65 years | 5 Participants | 4 Participants | 6 Participants | 6 Participants | 21 Participants |
| Body Mass Index (BMI) | 31.142 kg/m^2 STANDARD_DEVIATION 4.7113 | 30.985 kg/m^2 STANDARD_DEVIATION 5.5766 | 29.927 kg/m^2 STANDARD_DEVIATION 5.1504 | 31.146 kg/m^2 STANDARD_DEVIATION 4.5838 | 30.798 kg/m^2 STANDARD_DEVIATION 4.9778 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 15 Participants | 12 Participants | 12 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 10 Participants | 12 Participants | 11 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fasting Plasma Glucose | 194.3 mg/dL STANDARD_DEVIATION 50.86 | 170.3 mg/dL STANDARD_DEVIATION 44.28 | 182.8 mg/dL STANDARD_DEVIATION 40.97 | 184.7 mg/dL STANDARD_DEVIATION 50.87 | 182.9 mg/dL STANDARD_DEVIATION 46.93 |
| Haemoglobin A1c (HbA1c) | 7.95 % STANDARD_DEVIATION 0.837 | 8.01 % STANDARD_DEVIATION 0.713 | 7.82 % STANDARD_DEVIATION 0.563 | 8.24 % STANDARD_DEVIATION 0.831 | 8.00 % STANDARD_DEVIATION 0.747 |
| Previous Metformin experience Had Abdominal side effects from prior Metformin | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 12 Participants |
| Previous Metformin experience No Abdominal side effects from prior Metformin | 18 Participants | 20 Participants | 17 Participants | 16 Participants | 71 Participants |
| Previous Metformin experience No Previous Experience | 4 Participants | 1 Participants | 5 Participants | 3 Participants | 13 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 | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 Participants | 6 Participants | 16 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 | 22 Participants | 20 Participants | 19 Participants | 16 Participants | 77 Participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 13 Participants | 10 Participants | 51 Participants |
| Sex: Female, Male Male | 9 Participants | 12 Participants | 11 Participants | 13 Participants | 45 Participants |
| Weight | 87.049 kg STANDARD_DEVIATION 17.3747 | 88.584 kg STANDARD_DEVIATION 19.4687 | 84.493 kg STANDARD_DEVIATION 19.8622 | 86.777 kg STANDARD_DEVIATION 16.57 | 86.745 kg STANDARD_DEVIATION 18.1696 |
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 / 24 | 0 / 25 | 0 / 24 | 0 / 23 |
| other Total, other adverse events | 3 / 24 | 3 / 25 | 3 / 24 | 5 / 23 |
| serious Total, serious adverse events | 1 / 24 | 1 / 25 | 0 / 24 | 1 / 23 |
Outcome results
Primary
Change From Baseline to Day 28 in Absolute Plasma Glucose Area Under the Curve (AUC) 0-3hr
The primary endpoint for NS 0100 01 was the absolute plasma glucose AUC (0-3 hr) change from Day 1 to Day 28.
Time frame: 0, 15min, 30min, 45min, 1hr, 1.5hrs, 2hrs, 2.5hrs and 3 hrs
Population: Mixed Model Inferential Statistical Analysis of Plasma Glucose AUC change from day 1-day 28 Evaluable Population (n=73)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC125 | Change From Baseline to Day 28 in Absolute Plasma Glucose Area Under the Curve (AUC) 0-3hr | -18.005 mg*hrs/dL | Standard Deviation 142.8374 |
| FDC250 | Change From Baseline to Day 28 in Absolute Plasma Glucose Area Under the Curve (AUC) 0-3hr | -45.029 mg*hrs/dL | Standard Deviation 114.6701 |
| FDC500 | Change From Baseline to Day 28 in Absolute Plasma Glucose Area Under the Curve (AUC) 0-3hr | -64.010 mg*hrs/dL | Standard Deviation 146.0917 |
| Control | Change From Baseline to Day 28 in Absolute Plasma Glucose Area Under the Curve (AUC) 0-3hr | -141.848 mg*hrs/dL | Standard Deviation 194.93 |
p-value: 0.0435ANCOVA
p-value: 0.065ANCOVA
p-value: 0.1216ANCOVA
Secondary
Change From Baseline to Day 28 in Fasting Plasma Insulin Concentration
Effect on fasting plasma insulin concentrations across fixed-dose leucine and metformin combination treatments or the standard metformin reference treatment was evaluated.
Time frame: Baseline, Day 28
Population: Mixed Model Inferential Statistical Analysis of Plasma Insulin AUC and Incremental AUC change from day 1-day 28 Evaluable Population (n=73). Some collected were not viable. So, the total samples collected were still the same but since they could not be included in the analysis the exact number analyzed is referenced.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC125 | Change From Baseline to Day 28 in Fasting Plasma Insulin Concentration | -2.06 h*uIU/mL | Standard Deviation 6.652 |
| FDC250 | Change From Baseline to Day 28 in Fasting Plasma Insulin Concentration | -0.74 h*uIU/mL | Standard Deviation 4.069 |
| FDC500 | Change From Baseline to Day 28 in Fasting Plasma Insulin Concentration | 0.20 h*uIU/mL | Standard Deviation 7.278 |
| Control | Change From Baseline to Day 28 in Fasting Plasma Insulin Concentration | -1.03 h*uIU/mL | Standard Deviation 7.694 |
p-value: 0.9789ANCOVA
p-value: 0.841ANCOVA
p-value: 0.748ANCOVA
Secondary
Change From Baseline to Day 28 in Incremental Plasma Glucose Area Under the Curve (AUC)
The baseline incremental (baseline-subtracted) glucose AUC0-3h was evaluated for treatment differences at baseline.
Time frame: Baseline, Day 28
Population: Mixed Model Inferential Statistical Analysis of Incremental Plasma Glucose AUC change from day 1-day 28 Evaluable Population (n=73)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC125 | Change From Baseline to Day 28 in Incremental Plasma Glucose Area Under the Curve (AUC) | -2.338 mg*hrs/dL | Standard Deviation 60.2834 |
| FDC250 | Change From Baseline to Day 28 in Incremental Plasma Glucose Area Under the Curve (AUC) | -17.614 mg*hrs/dL | Standard Deviation 93.1243 |
| FDC500 | Change From Baseline to Day 28 in Incremental Plasma Glucose Area Under the Curve (AUC) | -23.061 mg*hrs/dL | Standard Deviation 64.629 |
| Control | Change From Baseline to Day 28 in Incremental Plasma Glucose Area Under the Curve (AUC) | -29.604 mg*hrs/dL | Standard Deviation 86.1126 |
p-value: 0.8867ANCOVA
p-value: 0.7641ANCOVA
p-value: 0.2518ANCOVA
Secondary
Change In 7-Point Glucose Profiles
The meal induced glucose change in pre-meal and post-meal glucose were measured 7 times during the day. Subjects self-monitored blood glucose (preprandial and postprandial) concentrations at least 7 times, including before and 1 to 2 hours after breakfast, lunch, dinner, and snacks). For each study day, the pre-meal values from the 7 point test for each subject were averaged to generate a single pre-meal glucose value. Similarly, for each study day the post-meal values from the 7-point test for each subject were averaged to generate a single post-meal glucose value. The average change from baseline (i.e., \[(Mean Pre/Post-meal value at Day 28 - Mean Pre/Post-meal value at Baseline) + (Mean Pre/Post-meal value at Day 21- Mean Pre/Post-meal value at Baseline) + (Mean Pre/Post-meal value at Day 7- Mean Pre/Post-meal value at Baseline)\]/ 3) over multiple time points listed in Time Frame. The mean pre-meal and post-meal values for baseline, day7, day 21 and day28 were used for comparison.
Time frame: Baseline, Day 7, Day 21, Day 28
Population: Mixed Model Inferential Statistical Analysis of 7 point glucose change from day 1-day 28 Evaluable Population (n=73). Some of the samples collected were not viable and could not be included in the analysis. The total samples collected were still the same but since they could not be included in the analysis the exact number analyzed is referenced.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC125 | Change In 7-Point Glucose Profiles | 28 day change in Post-meal Glucose Level | -15.98 mg/dL | Standard Deviation 33.966 |
| FDC125 | Change In 7-Point Glucose Profiles | 28 day change in Pre-meal Glucose Level | -6.50 mg/dL | Standard Deviation 32.343 |
| FDC250 | Change In 7-Point Glucose Profiles | 28 day change in Post-meal Glucose Level | 10.56 mg/dL | Standard Deviation 44.944 |
| FDC250 | Change In 7-Point Glucose Profiles | 28 day change in Pre-meal Glucose Level | -8.96 mg/dL | Standard Deviation 61.561 |
| FDC500 | Change In 7-Point Glucose Profiles | 28 day change in Pre-meal Glucose Level | -25.51 mg/dL | Standard Deviation 42.198 |
| FDC500 | Change In 7-Point Glucose Profiles | 28 day change in Post-meal Glucose Level | -34.25 mg/dL | Standard Deviation 77.268 |
| Control | Change In 7-Point Glucose Profiles | 28 day change in Post-meal Glucose Level | -50.33 mg/dL | Standard Deviation 60.756 |
| Control | Change In 7-Point Glucose Profiles | 28 day change in Pre-meal Glucose Level | -53.78 mg/dL | Standard Deviation 45.488 |
p-value: 0.011ANCOVA
p-value: 0.0152ANCOVA
p-value: 0.0284ANCOVA
p-value: 0.1273ANCOVA
p-value: 0.0085ANCOVA
p-value: 0.1289ANCOVA
Secondary
Change in Fasting Plasma Glucose
Change in fasting plasma glucose for the fixed dose leucine and metformin combination treatments A, B and C was evaluated.
Time frame: Baseline, Day 28
Population: Mixed Model Inferential Statistical Analysis of Fasting Plasma Glucose change from day 1-day 28 Evaluable Population (n=73)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC125 | Change in Fasting Plasma Glucose | -6.8 mg/dL | Standard Deviation 36.91 |
| FDC250 | Change in Fasting Plasma Glucose | -9.7 mg/dL | Standard Deviation 26.5 |
| FDC500 | Change in Fasting Plasma Glucose | -13.4 mg/dL | Standard Deviation 38.55 |
| Control | Change in Fasting Plasma Glucose | -36.0 mg/dL | Standard Deviation 47.36 |
p-value: 0.0179ANCOVA
p-value: 0.0736ANCOVA
p-value: 0.0475ANCOVA
Secondary
Change in Hemoglobin A1c (HbA1c)
Changes in HbA1c which is a marker of long-term glucose control was assessed.
Time frame: Baseline, Day 28
Population: Mixed Model Inferential Statistical Analysis of HbA1c change from day 1-day 28 Evaluable Population (n=73)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC125 | Change in Hemoglobin A1c (HbA1c) | 0.11 percent | Standard Deviation 0.448 |
| FDC250 | Change in Hemoglobin A1c (HbA1c) | -0.16 percent | Standard Deviation 0.485 |
| FDC500 | Change in Hemoglobin A1c (HbA1c) | -0.01 percent | Standard Deviation 0.442 |
| Control | Change in Hemoglobin A1c (HbA1c) | -0.23 percent | Standard Deviation 0.607 |
p-value: 0.0089ANCOVA
p-value: 0.376ANCOVA
p-value: 0.0578ANCOVA
Secondary
Change in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR)
Effect on insulin sensitivity across fixed-dose leucine and metformin combination treatments or the standard metformin reference treatment.
Time frame: Baseline, Day 28
Population: Mixed Model Inferential Statistical Analysis of HOMA-IR. Some of the samples collected were not viable and could not be included in the analysis. So, the total samples collected were still the same but since they could not be included in the analysis the exact number analyzed is referenced.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC125 | Change in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | -0.31 HOMA units | Standard Deviation 1.01 |
| FDC250 | Change in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | -0.14 HOMA units | Standard Deviation 0.548 |
| FDC500 | Change in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | 0.11 HOMA units | Standard Deviation 0.958 |
| Control | Change in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | -0.18 HOMA units | Standard Deviation 1.017 |
Comparison: The HOMA Calculator,is an algorithm that takes account of variations in hepatic and peripheral glucose resistance, increases in insulin secretion curve for plasma glucose concentrations above 10 mmol/L (180 mg/dL), and contribution of circulating proinsulin (eg, C-peptide) to estimate steady state beta cell function (%HOMA-B) and insulin sensitivity (%HOMA-S), as percentages of a normal reference population. %HOMA-IR was analyzed on a logarithmic scale (natural logarithmic transformation).p-value: 0.2177ANCOVA
p-value: 0.4144ANCOVA
p-value: 0.3117ANCOVA
Secondary
Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr
Change in meal tolerance test insulin area under the curve (0-2 hr) from Day 1 to Day 28 for fixed-dose leucine and metformin combination treatments.
Time frame: Baseline,Day 28
Population: Mixed Model Inferential Statistical Analysis of Plasma Insulin AUC and Incremental AUC change from day 1-day 28 Evaluable Population (n=73). Some samples collected were not viable. The total samples collected were still the same but since they couldn't included in the analysis, exact number analyzed is referenced.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC125 | Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr | Plasma Insulin Absolute | -0.19 h*ulU/ml | Standard Deviation 74.531 |
| FDC125 | Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr | Plasma Insulin Incremental | 4.18 h*ulU/ml | Standard Deviation 67.12 |
| FDC250 | Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr | Plasma Insulin Incremental | -4.25 h*ulU/ml | Standard Deviation 29.514 |
| FDC250 | Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr | Plasma Insulin Absolute | -5.64 h*ulU/ml | Standard Deviation 31.36 |
| FDC500 | Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr | Plasma Insulin Absolute | -9.59 h*ulU/ml | Standard Deviation 34.987 |
| FDC500 | Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr | Plasma Insulin Incremental | -9.99 h*ulU/ml | Standard Deviation 27.956 |
| Control | Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr | Plasma Insulin Absolute | -18.06 h*ulU/ml | Standard Deviation 35.473 |
| Control | Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr | Plasma Insulin Incremental | -15.91 h*ulU/ml | Standard Deviation 26.72 |
p-value: 0.3143ANCOVA
p-value: 0.5677ANCOVA
p-value: 0.8407ANCOVA