Diabetes Mellitus, Type 2
Conditions
Brief summary
The aim of this pilot study is to assess the safety and preliminary efficacy of 5-ALA - SFC at doses up to 200 mg per day in subjects with type II diabetes.
Detailed description
The primary objective is to assess the safety of 5-ALA - SFC at doses up to 200 mg per day in subjects with type II diabetes mellitus. Safety will be assessed by the incidence of adverse events and clinically significant laboratory results. The secondary objective is to assess the efficacy of 5-ALA-SFC at doses up to 200 mg per day on glycemic control in subjects with type II diabetes mellitus. Efficacy measures will include fasting plasma glucose level, HbA1c level, lipid profile, and body weight.
Interventions
DRUG5-ALA-SFC
Study product will be in the form of white-opaque capsules for oral administration, containing either 50, 75, or 100 mg of active 5-ALA - SFC
DRUGPlacebo
Sponsors
SBI Pharmaceuticals Co, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males and females residing in Bahrain aged 20 to 75 years old 2. Otherwise in good health in the opinion of the investigator based on results of medical history, physical exam and laboratory assessments 3. Diagnosed with type II diabetes mellitus with HbA1c \>6.5 and \<10% which is uncontrolled despite the use of one or more glycemia-lowering drugs 4. BMI ≤44 kg/m2 5. Sitting BP ≤ 160/100mm Hg 6. Sleep apnea screening is negative 7. Ophthalmological exam is within normal limits as judged by the investigator. If findings are observed, they must be judged as not clinically significant. 8. Female subjects are not pregnant, not breast-feeding, and if of childbearing potential, have agreed to use an acceptable method of birth control
Exclusion criteria
1. Liver dysfunction defined as liver function tests \>1.5 times upper limit of normal 2. Renal dysfunction defined as BUN and/or serum creatinine \>1.5 times upper limit of normal and/or eGFR \<30 ml/min/1.73 m2 3. History of any life-threatening disease, cardiovascular disease, viral hepatitis, porphyria or hemochromatosis 4. Allergy to ALA, SFC, or any other component of study product 5. Use of insulin for management of serum glucose 6. Hypoglycemic event within the previous 3 months, defined as serum glucose levels less than 70 mg/dL 7. History of sickle cell anemia disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects With Adverse Events as a Measure of Safety and Tolerability | Week 2, Week 4, Week 12 | The objective of the current study was to investigate the safety and preliminary efficacy of doses up to 200 mg 5-ALA - SFC in a population of patients with type 2 diabetes mellitus living in Bahrain. |
| Change From Baseline in Fasting Blood Glucose | Baseline, Week 2, Week 4, Week 12 | The objective of the current study was to investigate the safety and preliminary efficacy of doses up to 200 mg 5-ALA - SFC in a population of patients with type 2 diabetes mellitus living in Bahrain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c | Baseline, Week 2, Week 4, Week 12 | Change from baseline in HbA1c % |
| Change From Baseline in Total Cholesterol (Component of Lipid Profile) | Baseline, Week 6, Week 12 | Change from baseline measured at week 6 and week 12 only |
| Change From Baseline in 2 Hour Post Meal Glucose Level | Baseline, Week 2, Week 4, Week 12 | Change from baseline in blood glucose levels 2 hours after breakfast |
| Change From Baseline in HDL (Component of Lipid Profile) | Baseline, Week 6, Week 12 | Change from baseline measured at week 6 and week 12 only |
| Change From Baseline in Triglycerides (Component of Lipid Profile) | Baseline, Week 6, Week 12 | Change from baseline measured at week 6 and week 12 only |
| Change From Baseline LDL (Component of Lipid Profile) | Baseline, Week 6, Week 12 | Change from baseline measured at week 6 and week 12 only |
| Change From Baseline in Body Weight | Baseline, Week 6, Week 12 | Change from baseline measured at week 6 and week 12 only |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5-ALA-SFC Study product administration will be as follows:
Beginning Week 0: 1 capsule of 50mg 5-ALA-SFC twice per day for 2 weeks Beginning Week 2: 1 capsule of 75mg 5-ALA-SFC twice per day for 2 weeks Beginning Week 4: 1 capsule of 100mg 5-ALA-SFC twice per day for 8 weeks
5-ALA-SFC: Study product will be in the form of white-opaque capsules for oral administration, containing either 50, 75, or 100 mg of active 5-ALA - SFC | 35 |
| Placebo Study matching placebo administration will be as follows:
Beginning Week 0: 1 capsule twice per day for 2 weeks Beginning Week 2: 1 capsule twice per day for 2 weeks Beginning Week 4: 1 capsule twice per day for 8 weeks
Placebo | 15 |
| Total | 50 |
Baseline characteristics
| Characteristic | Placebo | 5-ALA-SFC | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 33 Participants | 48 Participants |
| Age, Continuous | 51.9 years STANDARD_DEVIATION 5.07 | 52.4 years STANDARD_DEVIATION 6.51 | 52.2 years STANDARD_DEVIATION 6.07 |
| Region of Enrollment Bahrain | 15 participants | 35 participants | 50 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 13 Participants | 33 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 18 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 6 / 35 | 14 / 35 | 16 / 35 | 3 / 18 | 4 / 18 | 5 / 18 |
| serious Total, serious adverse events | 1 / 35 | 0 / 35 | 0 / 35 | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Change From Baseline in Fasting Blood Glucose
The objective of the current study was to investigate the safety and preliminary efficacy of doses up to 200 mg 5-ALA - SFC in a population of patients with type 2 diabetes mellitus living in Bahrain.
Time frame: Baseline, Week 2, Week 4, Week 12
Population: Intent-to-Treat Population (ITT) included all subjects who took at least one dose of study product and had at least one post-baseline efficacy evaluation. Change from Baseline was calculated as the mean for the visit compared to baseline mean for only the subjects with a result for that visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5-ALA-SFC Through Week 2 (50 mg 2x/Day) | Change From Baseline in Fasting Blood Glucose | 2.3 mg/dL | Standard Error 3.4 |
| 5-ALA-SFC Through Week 4 (75 mg 2x/Day) | Change From Baseline in Fasting Blood Glucose | -0.2 mg/dL | Standard Error 4.9 |
| 5-ALA-SFC Through Week 12 (100 mg 2x/Day) | Change From Baseline in Fasting Blood Glucose | -3.0 mg/dL | Standard Error 4.4 |
| Placebo Through Week 2 | Change From Baseline in Fasting Blood Glucose | -7.3 mg/dL | Standard Error 5.2 |
| Placebo Through Week 4 | Change From Baseline in Fasting Blood Glucose | -0.8 mg/dL | Standard Error 7.2 |
| Placebo Through Week 12 | Change From Baseline in Fasting Blood Glucose | -4.2 mg/dL | Standard Error 5.9 |
Primary
Subjects With Adverse Events as a Measure of Safety and Tolerability
The objective of the current study was to investigate the safety and preliminary efficacy of doses up to 200 mg 5-ALA - SFC in a population of patients with type 2 diabetes mellitus living in Bahrain.
Time frame: Week 2, Week 4, Week 12
Population: Safety population included all subjects who took at least one dose of study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5-ALA-SFC Through Week 2 (50 mg 2x/Day) | Subjects With Adverse Events as a Measure of Safety and Tolerability | 6 Participants |
| 5-ALA-SFC Through Week 4 (75 mg 2x/Day) | Subjects With Adverse Events as a Measure of Safety and Tolerability | 8 Participants |
| 5-ALA-SFC Through Week 12 (100 mg 2x/Day) | Subjects With Adverse Events as a Measure of Safety and Tolerability | 2 Participants |
| Placebo Through Week 2 | Subjects With Adverse Events as a Measure of Safety and Tolerability | 3 Participants |
| Placebo Through Week 4 | Subjects With Adverse Events as a Measure of Safety and Tolerability | 1 Participants |
| Placebo Through Week 12 | Subjects With Adverse Events as a Measure of Safety and Tolerability | 1 Participants |
Secondary
Change From Baseline in 2 Hour Post Meal Glucose Level
Change from baseline in blood glucose levels 2 hours after breakfast
Time frame: Baseline, Week 2, Week 4, Week 12
Population: Intent-to-Treat Population (ITT) included all subjects who took at least one dose of study product and had at least one post-baseline efficacy evaluation. Change from Baseline was calculated as the mean for the visit compared to baseline mean for only the subjects with a result for that visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5-ALA-SFC Through Week 2 (50 mg 2x/Day) | Change From Baseline in 2 Hour Post Meal Glucose Level | -0.2 mg/dL | Standard Error 5.1 |
| 5-ALA-SFC Through Week 4 (75 mg 2x/Day) | Change From Baseline in 2 Hour Post Meal Glucose Level | -12.9 mg/dL | Standard Error 6.1 |
| 5-ALA-SFC Through Week 12 (100 mg 2x/Day) | Change From Baseline in 2 Hour Post Meal Glucose Level | -8.5 mg/dL | Standard Error 9.8 |
| Placebo Through Week 2 | Change From Baseline in 2 Hour Post Meal Glucose Level | -26.5 mg/dL | Standard Error 7.8 |
| Placebo Through Week 4 | Change From Baseline in 2 Hour Post Meal Glucose Level | -18.8 mg/dL | Standard Error 9.9 |
| Placebo Through Week 12 | Change From Baseline in 2 Hour Post Meal Glucose Level | -33.0 mg/dL | Standard Error 14.2 |
Secondary
Change From Baseline in Body Weight
Change from baseline measured at week 6 and week 12 only
Time frame: Baseline, Week 6, Week 12
Population: Intent-to-Treat Population (ITT) included all subjects who took at least one dose of study product and had at least one post-baseline efficacy evaluation. Change from Baseline was calculated as the mean for the visit compared to baseline mean for only the subjects with a result for that visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5-ALA-SFC Through Week 2 (50 mg 2x/Day) | Change From Baseline in Body Weight | -0.1 kg | Standard Error 0.5 |
| 5-ALA-SFC Through Week 4 (75 mg 2x/Day) | Change From Baseline in Body Weight | -0.2 kg | Standard Error 0.3 |
| 5-ALA-SFC Through Week 12 (100 mg 2x/Day) | Change From Baseline in Body Weight | -0.3 kg | Standard Error 0.7 |
| Placebo Through Week 2 | Change From Baseline in Body Weight | -0.8 kg | Standard Error 0.4 |
Secondary
Change From Baseline in HbA1c
Change from baseline in HbA1c %
Time frame: Baseline, Week 2, Week 4, Week 12
Population: Intent-to-Treat Population (ITT) included all subjects who took at least one dose of study product and had at least one post-baseline efficacy evaluation. Change from Baseline was calculated as the mean for the visit compared to baseline mean for only the subjects with a result for that visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5-ALA-SFC Through Week 2 (50 mg 2x/Day) | Change From Baseline in HbA1c | -0.2 percentage of HbA1c | Standard Error 0.1 |
| 5-ALA-SFC Through Week 4 (75 mg 2x/Day) | Change From Baseline in HbA1c | -0.3 percentage of HbA1c | Standard Error 0.1 |
| 5-ALA-SFC Through Week 12 (100 mg 2x/Day) | Change From Baseline in HbA1c | -0.7 percentage of HbA1c | Standard Error 0.2 |
| Placebo Through Week 2 | Change From Baseline in HbA1c | -0.5 percentage of HbA1c | Standard Error 0.2 |
| Placebo Through Week 4 | Change From Baseline in HbA1c | -0.5 percentage of HbA1c | Standard Error 0.2 |
| Placebo Through Week 12 | Change From Baseline in HbA1c | -0.5 percentage of HbA1c | Standard Error 0.2 |
Secondary
Change From Baseline in HDL (Component of Lipid Profile)
Change from baseline measured at week 6 and week 12 only
Time frame: Baseline, Week 6, Week 12
Population: Intent-to-Treat Population (ITT) included all subjects who took at least one dose of study product and had at least one post-baseline efficacy evaluation. Change from Baseline was calculated as the mean for the visit compared to baseline mean for only the subjects with a result for that visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5-ALA-SFC Through Week 2 (50 mg 2x/Day) | Change From Baseline in HDL (Component of Lipid Profile) | -0.8 mg/dL | Standard Error 1 |
| 5-ALA-SFC Through Week 4 (75 mg 2x/Day) | Change From Baseline in HDL (Component of Lipid Profile) | 0.5 mg/dL | Standard Error 1 |
| 5-ALA-SFC Through Week 12 (100 mg 2x/Day) | Change From Baseline in HDL (Component of Lipid Profile) | -1.6 mg/dL | Standard Error 1.4 |
| Placebo Through Week 2 | Change From Baseline in HDL (Component of Lipid Profile) | -1.1 mg/dL | Standard Error 1.4 |
Secondary
Change From Baseline in Total Cholesterol (Component of Lipid Profile)
Change from baseline measured at week 6 and week 12 only
Time frame: Baseline, Week 6, Week 12
Population: Intent-to-Treat Population (ITT) included all subjects who took at least one dose of study product and had at least one post-baseline efficacy evaluation. Change from Baseline was calculated as the mean for the visit compared to baseline mean for only the subjects with a result for that visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5-ALA-SFC Through Week 2 (50 mg 2x/Day) | Change From Baseline in Total Cholesterol (Component of Lipid Profile) | -5.2 mg/dL | Standard Error 3.7 |
| 5-ALA-SFC Through Week 4 (75 mg 2x/Day) | Change From Baseline in Total Cholesterol (Component of Lipid Profile) | 6.8 mg/dL | Standard Error 3.5 |
| 5-ALA-SFC Through Week 12 (100 mg 2x/Day) | Change From Baseline in Total Cholesterol (Component of Lipid Profile) | -7.6 mg/dL | Standard Error 5.5 |
| Placebo Through Week 2 | Change From Baseline in Total Cholesterol (Component of Lipid Profile) | -0.1 mg/dL | Standard Error 5 |
Secondary
Change From Baseline in Triglycerides (Component of Lipid Profile)
Change from baseline measured at week 6 and week 12 only
Time frame: Baseline, Week 6, Week 12
Population: Intent-to-Treat Population (ITT) included all subjects who took at least one dose of study product and had at least one post-baseline efficacy evaluation. Change from Baseline was calculated as the mean for the visit compared to baseline mean for only the subjects with a result for that visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5-ALA-SFC Through Week 2 (50 mg 2x/Day) | Change From Baseline in Triglycerides (Component of Lipid Profile) | -1.3 mg/dL | Standard Error 14.6 |
| 5-ALA-SFC Through Week 4 (75 mg 2x/Day) | Change From Baseline in Triglycerides (Component of Lipid Profile) | 3.2 mg/dL | Standard Error 11.1 |
| 5-ALA-SFC Through Week 12 (100 mg 2x/Day) | Change From Baseline in Triglycerides (Component of Lipid Profile) | 4.5 mg/dL | Standard Error 21.1 |
| Placebo Through Week 2 | Change From Baseline in Triglycerides (Component of Lipid Profile) | 11.9 mg/dL | Standard Error 15.4 |
Secondary
Change From Baseline LDL (Component of Lipid Profile)
Change from baseline measured at week 6 and week 12 only
Time frame: Baseline, Week 6, Week 12
Population: Intent-to-Treat Population (ITT) included all subjects who took at least one dose of study product and had at least one post-baseline efficacy evaluation. Change from Baseline was calculated as the mean for the visit compared to baseline mean for only the subjects with a result for that visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5-ALA-SFC Through Week 2 (50 mg 2x/Day) | Change From Baseline LDL (Component of Lipid Profile) | -2.9 mg/dL | Standard Error 3.2 |
| 5-ALA-SFC Through Week 4 (75 mg 2x/Day) | Change From Baseline LDL (Component of Lipid Profile) | 7.6 mg/dL | Standard Error 3.3 |
| 5-ALA-SFC Through Week 12 (100 mg 2x/Day) | Change From Baseline LDL (Component of Lipid Profile) | -11.8 mg/dL | Standard Error 4.7 |
| Placebo Through Week 2 | Change From Baseline LDL (Component of Lipid Profile) | -4.0 mg/dL | Standard Error 4.6 |