To Investigate the Safety, Tolerability and Pharmacodynamics of GSK2890457 in Healthy Volunteers and Subjects With Type 2 Diabetes

Study at a glance

From the registry record, last updated by the sponsor on 13 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Double-blind [Sponsor Unblinded], Randomized, Placebo-controlled, Staggered-parallel Study to Investigate the Safety, Tolerability, and Pharmacodynamics of GSK2890457 in Healthy Volunteers and Subjects With Type 2 Diabetes

ClinicalTrials.gov ID

NCT01725126

Acronym / sponsor ID

116623

Conditions

Obesity

Keywords

metformin, diabetes, obesity, liraglutide

Phase

Phase 2

Study type

Interventional

Recruitment status

Completed

Enrolment

53 participants (actual)

Lead sponsor

GlaxoSmithKlineIndustry (pharma, biotech, devices)

Study start

10 Feb 2013 (actual)

Primary completion

12 Sep 2013 (actual)

Study completion

12 Sep 2013 (actual)

First posted

12 Nov 2012 (estimated)

Results

Posted 23 Oct 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

Double blind (participant, investigator)

Number of arms

6

Who may qualify

Ages

18 to 70 years

Sex

All

Healthy volunteers

Accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A

   Time frame: Up to Follow-up (8 weeks)

   An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5.

2. Number of Participants With Any AE, SAE or Death During Part B and Part C

   Time frame: Up to Follow-up (8 weeks)

   An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as ALT >=3 x ULN, and total bilirubin >=2 x ULN or international normalized ratio >1.5.

3. Number of Participants With Any Hypoglycemic Events During Part A

   Time frame: Up to Follow-up (8 weeks)

   Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of complete blood count (CBG) or plasma glucose value of <50 milligram per deciliter (mg/dL) for Part A or <70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values <70 mg/dL as a physiological response to altered food intake (e.g., fasting).

4. Number of Participants With Any Hypoglycemic Events During Part B and Part C

   Time frame: Up to Follow-up (8 weeks)

   Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of CBG or plasma glucose value of <50 mg/dL for Part A or <70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values <70 mg/dL as a physiological response to altered food intake (e.g., fasting).

5. Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A

   Time frame: Baseline (Day 1, Randomization) up to Day 42

   The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

6. Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C

   Time frame: Baseline (Day -1) up to Day 42

   The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

7. Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A

   Time frame: Baseline (Day 1, Randomization) up to Day 42

   The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at on Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

8. Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C

   Time frame: Baseline (Day -1) up to Day 42

   The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

9. Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A

   Time frame: Baseline (Day 1, Randomization) up to Day 42

   The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

10. Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

11. Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

12. Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

13. Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

14. Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

15. Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study

    Time frame: Baseline (Day -1) and Day 42

    The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

16. Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) and Day 42

    The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

17. Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) and Day 42

    The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

18. Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

19. Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

20. Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

21. Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

22. Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

23. Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

24. Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

25. Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

26. Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

27. Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

28. Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

29. Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

30. Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

31. Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A

    Time frame: Up to Day 42

    The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as rare, trace, +1, 2+, RBC's and WBC's as <1, 1, 2, 3 and 4. Protein concentration ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. Trace was the highest concentration for occult blood. Bacteria concentration ranged from rare to moderate, where rare indicated lowest concentration and moderate indicated highest concentration. Ketones ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. RBC and WBC ranged from <1 to 4, where <1 indicated lowest concentration and 4 indicated highest concentration. Highest concentration indicated worse outcome.

32. Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B

    Time frame: Up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as few, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, and 20-40. Few was the highest concentration of bacteria. Occult blood ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Epithelial cell ranged from 0-5 to 10-20, 0-5 indicated lowest and 10-20 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-5 was highest concentration for hyaline casts. Ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. RBC and WBC ranged from 0-3 to 20-40, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome.

33. Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C

    Time frame: Up to Day 42

    The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. The participants were categorized as few, many, moderate, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, 20-40, 40-60. Protein and ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Bacteria and uric acid crystals ranged from few to moderate, few indicated lowest and moderate indicated highest concentration. Trace was the highest concentration of occult blood. Epithelial cells ranged from 0-5 to >10, 0-5 indicated lowest and >10 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-1 was highest concentration for hyaline casts. RBC and WBC ranged from 0-3 to 40-60, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome.

34. Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A

    Time frame: Up to Day 42

    Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Da y 1, Day 7, Day 14, Day 28 and Day 42.

35. Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C

    Time frame: Up to Day 42

    Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42.

36. Mean pH Values of Urine During the Double-blind Treatment Period of Part A

    Time frame: up to Day 42

    Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day 1, Day 7, Day 14, Day 28 and Day 42.

37. Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C

    Time frame: Up to Day 42

    Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day -1, Day 7, Day 14, Day 28 and Day 42.

38. Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

39. Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

40. Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

41. Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Day 42

    Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

42. Change From Baseline in Electrocardiogram (ECG) Intervals During Part A

    Time frame: Baseline (Day 1, Randomization) up to Follow-up (Day 56)

    Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QT duration corrected for HR by Fridericia's formula (QTcF) and QT duration corrected for HR by Bazett's formula (QTcB intervals. The assessments were done at Day 1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

43. Change From Baseline in ECG Intervals During Part B and C

    Time frame: Baseline (Day -1) up to Follow-up (Day 56)

    Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QTcB, QTcF and RR intervals. The assessments were done at Day -1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

44. Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A

    Time frame: Baseline (Day 1, Randomization) up to Day 42

    The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14 and 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

45. Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -2) up to Day 41

    The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day -2. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14, 28 and 41) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

46. Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1 and Day 1) up to Day 42

    During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values.

47. Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1 and Day 1) up to Day 42

    During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. Percent change was calculated by multiplying the change from Baseline value with 100. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values.

48. Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) and Day 42

    AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean glucose AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast. Adjusted mean is reported as least square (LS) mean.

49. Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) and Day 42 of Part B and C

    Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean.

50. Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) and Day 42

    Two fasting samples 5 minutes apart were taken for insulin. Baseline insulin level was the average of the 2 fasting samples. For insulin weighted mean AUC (0-4 hour) and weighted mean AUC (0-24 hour) was calculated for Baseline (Day -1) and end of treatment (Day 42). AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean insulin AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast.

51. Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) and Day 42

    Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean.

52. Change From Baseline in Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR]) During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) and Day 42

    HOMA-IR was calculated from the Day -1 and Day 42 fasting glucose and insulin values using dataset generated from the HOMA-2 model. It contained the estimates for HOMA-% insulin sensitivity (S) for pairs of fasting glucose and fasting insulin values. Study data was merged with the HOMA dataset by glucose and insulin. HOMA-IR was calculated as 100/HOMA-%S. HOMA-IR was not determined for any values outside the ranges of plasma glucose 3.5 to 25.0 mmol/L (63 - 450 mg/dL) and plasma insulin 20 to 400 pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.

53. Change From Baseline in Matsuda Index During the Double Blind-treatment Period of Part B and C

    Time frame: Baseline (Day -1) and Day 42

    The matsuda index was calculated from the Day -1 and Day 42 glucose and insulin results as 10,000 divided by (fasting plasma glucose x fasting plasma insulin x mean glucose at 0-2 hour post-dose x mean insulin at 0-2 hour post dose)^1/2, where glucose was measured in mmol/L and insulin in pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.

54. Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C

    Time frame: Baseline (Day -1) up to Follow-up (Day 56)

    The assessments were done at Day -1, Day 7, Day 14, Day 28, Day 42 and Follow-up Visit. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline (Day 7, 14, 28, 42 and Follow-up visit) values.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2017.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 27093610Hodge RJ, Paulik MA, Walker A, Boucheron JA, McMullen SL, Gillmor DS, Nunez DJ. Weight and Glucose Reduction Observed with a Combination of Nutritional Agents in Rodent Models Does Not Translate to Humans in a Randomized Clinical Trial with Healthy Volunteers and Subjects with Type 2 Diabetes. PLoS One. 2016 Apr 19;11(4):e0153151. doi: 10.1371/journal.pone.0153151. eCollection 2016.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
• Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

3 sites in 1 country: see every site and its status.