Comparison of Insulin Tregopil (IN-105) With Insulin Aspart in Type 2 Diabetes Mellitus Patients

• Sponsor: Biocon Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03430856
• Collaborator: (none)
• Enrollment: 143
• Location: 1
• Arms: 3
• Actual Duration (Months): 13.8
• Patients Per Site Per Month: 10.3

Study Details

Study Description

Brief Summary

This is an open label Phase II/III study to evaluate the efficacy and safety of test drug, Insulin Tregopil (IN-105) compared with Insulin Aspart (IAsp) in Type 2 Diabetes Mellitus patients. on stable dose of Metformin and insulin Glargine. The study will be conducted in 2 parts, Part I and Part II. The study duration will be approximately 37 weeks for Part I and for Part II of the study respectively

Condition or Disease	Intervention/Treatment	Phase
Type2 Diabetes Mellitus	Drug: Insulin Tregopil; Drug: Insulin Aspart	Phase 2/Phase 3

Detailed Description

Part I of the study is a Phase II multi-center, randomized, open label clinical study to evaluate the efficacy and safety of Insulin Tregopil (2 dose levels: 30 mg, 45 mg) compared with IAsp in the treatment of T2DM patients. Part II of the study is the Phase III, multi-center, randomized, open label clinical study to evaluate the efficacy and safety of Insulin Tregopil (30 mg or 45 mg based upon the outcome of Part I data) compared with IAsp in the treatment of T2DM patients. For Part I and Part II, the study duration will be approximately 37 weeks (3 weeks Screening, 8 weeks Run-in, 24 weeks Treatment, 2 weeks Safety follow-up). An Independent Data and Safety Monitoring Board (DSMB) will evaluate the data from Part I of the study. Part II of the study will be initiated after approval from the office of Drugs Controller General of India (DCGI) and Data Safety Monitoring Board (DSMB) recommendation based on review of data from Part I of the study. In both Part I and Part II of the study, T2DM patients with glycated hemoglobin (HbA1c) 7.5 to 10% (both inclusive), on stable dose of metformin ± oral antidiabetic drugs (OADs) ± basal insulin who are eligible for insulin glargine administration as per investigator discretion and who satisfy the selection criteria will be enrolled. The eligible patients will go through a Run-in period of 8 weeks. At the end of 8 weeks Run-in period, eligibility will be checked and patients will enter the treatment period of 24 weeks and will be allocated to 3 treatment arms (Part I) or randomized to 2 treatment arms (Part II); if found eligible for randomization. A total of 90 patients in part 1 and 268 patients in part 2 will be randomised to the treatment arms from approximately 40 centers in India.

Study Design

• Study Type: Interventional
• Actual Enrollment: 143 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Study is conducted in two parts. Part I has 3 arms and Part 2 has 2 arms.Study is conducted in two parts. Part I has 3 arms and Part 2 has 2 arms.
• Masking: None (Open Label)
• Masking Description: Open Label Trial
• Primary Purpose: Treatment
• Official Title: An Open Label, Multi-center, Randomized, Parallel Group Phase II/III Clinical Study to Evaluate the Efficacy and Safety of Insulin Tregopil (IN-105) Compared With Insulin Aspart in the Treatment of Patients With Type 2 Diabetes Mellitus on Stable Dose of Metformin and Insulin Glargine
• Actual Study Start Date: Dec 26, 2017
• Actual Primary Completion Date: Feb 6, 2019
• Actual Study Completion Date: Feb 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin Tregopil (IN-105) - 45mg Strength of each tablet is 15mg	Drug: Insulin Tregopil; Drug: Insulin Tregopil (IN-105) Mode of Administration: To be administered orally 10 ± 2 minutes prior to each major meal (breakfast, lunch and dinner) starting at the Randomization visit.; Other Names: IN-105
Experimental: Insulin Tregopil (IN-105) - 30mg Strength of each tablet is 15mg	Drug: Insulin Tregopil; Drug: Insulin Tregopil (IN-105) Mode of Administration: To be administered orally 10 ± 2 minutes prior to each major meal (breakfast, lunch and dinner) starting at the Randomization visit.; Other Names: IN-105
Active Comparator: Insulin Aspart Pre-filled pen: 100 U/L	Drug: Insulin Aspart; Drug: Insulin Aspart Mode of Administration: To be administered within 5 minutes prior to each major meal (breakfast, lunch and dinner) starting at the Randomization visit

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in HbA1c at 24 Weeks (Part 1) [Week 0, Week 24]

   The primary endpoint is change from baseline in HbA1c after 24 weeks of randomized treatment.

Secondary Outcome Measures

1. Change From Baseline in HbA1c at Week 12 (Part 1) [Week 0, Week 12]

   This secondary outcome is the change from baseline in HbA1c after 12 weeks of randomized treatment. For this endpoint baseline (Week 0) and Week 12 have been presented.

2. Participants Achieving HbA1c < 7% (Part 1) [Week 12, Week 24]

   Number of participants achieving HbA1c < 7% at Week 12 and Week 24.

3. Percentage of Participants With Hypoglycemia Events During 24-week Treatment Period (Part 1) [Week 0 through Week 24]

   A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤ 70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)]

4. Weight (Kgs) (Part 1) [Week 0 and Week 24]

   Change from Baseline in weight (kgs) to 24 weeks

5. Lipid Profile (Part 1) [24 weeks]

   Change from Baseline in lipid profile (triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol) to 24 weeks

6. Post-prandial Glucose (PPG) Excursion (Part 1) [Week 0, Week 24]

   Change from Baseline in the mean 60, 90, 120 minutes PPG excursions assessed from standardized test meal at Week 24.

7. Number of Participants With Treatment-Emergent Adverse Events (Part 1) [24 weeks]

   Includes participants who have experienced at least one treatment emergent adverse events over 24 weeks

8. Anti-drug Antibody Levels [24 weeks]

   Incidence and change from baseline in the relative levels of anti-drug antibody levels over 24 weeks

9. CGM [24 weeks]

   Area under the glucose curve below 70 mg/dL derived from CGM, applicable for only part II study

Other Outcome Measures

1. Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24 [Week 12, Week 24]

   Number of participants achieving HbA1c < 7% at Week 12 and Week 24 without reported clinically significant or severe hypoglycemic events between end of Week 8 and Week 24.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria

• Patients with an established diagnosis of T2DM and a duration of diabetes mellitus of at least 6 months at Screening based on criteria given below as per American Diabetes Association (ADA) 2017 guidelines: i. HbA1c ≥ 6.5% OR ii. FPG ≥ 126 mg/dL. (Fasting is defined as no caloric intake for at least 8 hours.) OR iii. 2-hour prandial glucose (PG) level of ≥ 200 mg/dL during an oral glucose tolerance test (OGTT).

• Stable dose of metformin (at least 1500 mg daily [daily dose of at least 1000 mg is permitted if intolerant to 1500 mg dose]) for a period of at least 3 months prior to Screening

• Eligible for initiation of or already receiving insulin glargine

• Hemoglobin ≥ 10.0 g/Dl

• HbA1c of 7.5% to 10.0 %

• Body mass index of 18.5 to 35.0 kg/m2

Key Exclusion Criteria

• Patients with T1DM

• Treatment with glucagon-like peptide 1 agonists within 12 weeks prior to Screening

• Ongoing treatment with OADs (eg, Thiazolidinediones) contraindicated or unapproved for combination treatment with insulin

• Presence of gastrointestinal (GI) disorders or conditions known to significantly alter the absorption of orally administered drugs or significantly alter upper GI or pancreatic function

• History of ≥2 episodes of severe hypoglycemia (as per ADA 2017) within the 6 months before Screening

• History of > 1 episode of hyperglycemic hyperosmolar coma or hospitalization for uncontrolled diabetes (eg, diabetic ketoacidosis); within the 6 months prior to Screening

• Clinically significant cardiovascular and/or cerebrovascular disease within 12 months before Screening including, but not limited to unstable angina, myocardial infarction, Class III or Class IV congestive heart failure according to the New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, pulmonary hypertension, cardiac surgery, coronary angioplasty, stroke or transient ischemic attack.

• Patients with the following secondary complications of diabetes:

1. Active proliferative retinopathy as confirmed by a dilated ophthalmoscopy (by the investigator, site ophthalmologist or an optometrist; as per standard site practice) within 6 months prior to Screening. ii. Renal dysfunction indicated by modification of diet in renal disease estimated glomerular filtration rate < 45 mL/min/1.73 m2 and/or diabetic nephropathy and/or clinical nephrotic syndrome at Screening. iii. History or presence of severe form of neuropathy or signs and symptoms of severe cardiac autonomic neuropathy. iv. Patients with non-traumatic amputation (at any time) or clinically significant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Diacon Hospital	Bangalore	Karnataka	India	560010

Sponsors and Collaborators

• Biocon Limited

Investigators

• Study Director: Subramanian Loganathan, MD, Biocon Research Limited

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 21, 2018

More Information

Publications

None provided.

• Responsible Party: Biocon Limited
• ClinicalTrials.gov Identifier: NCT03430856
• Other Study ID Numbers: TREGO-DM2-03-I-01
• First Posted: Feb 13, 2018
• Last Update Posted: May 15, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Biocon Limited: Oral insulin
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Aspart

Study Results

Participant Flow

Recruitment Details	Out of 20 sites, which were selected for recruitment, 19 sites enrolled subjects in the run-in period, of which 15 sites later assigned subjects to randomized treatment: India:20 sites
Pre-assignment Detail	The trial included an 8-week run-in period and a 24-week treatment period. During the run-in period, the subjects received insulin glargine along with metformin. In total, 143 subjects entered the run-in period, of these 52 subjects were run-in failures. Hence, 91 subjects were randomly assigned to each treatment arm.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Period Title: Overall Study
STARTED	31	30	30
Exposed	31	30	30
COMPLETED	29	27	29
NOT COMPLETED	2	3	1

Baseline Characteristics

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart	Total
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	Total of all reporting groups
Overall Participants	31	30	30	91
Age (Year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Year]	52.1 (9.49)	50.9 (9.44)	54.5 (8.18)	52.5 (9.08)
Sex: Female, Male (Count of Participants)
Female	15 48.4%	14 46.7%	14 46.7%	43 47.3%
Male	16 51.6%	16 53.3%	16 53.3%	48 52.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	31 100%	30 100%	30 100%	91 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
India	31 100%	30 100%	30 100%	91 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	68.54 (11.559)	68.88 (9.040)	67.76 (9.628)	68.39 (10.048)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	158.84 (7.987)	158.76 (9.268)	158.20 (9.321)	158.60 (8.776)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.13 (3.866)	27.39 (3.418)	27.13 (3.667)	27.22 (3.618)
Duration of T2DM (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.78 (7.867)	7.83 (7.715)	8.12 (6.788)	8.25 (7.404)
Glycosylated haemoglobin A1c (Percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of glycosylated haemoglobin]	8.23 (0.577)	8.10 (0.670)	8.07 (0.697)	8.13 (0.646)
OAD/Basal Insulin use at Screening Number of participants (%) (Count of Participants)
Metformin alone	4 12.9%	2 6.7%	0 0%	6 6.6%
Metformin + other OADs	6 19.4%	6 20%	7 23.3%	19 20.9%
Metformin + OADs + Basal insulin	18 58.1%	19 63.3%	19 63.3%	56 61.5%
Metformin - OADs + Basal insulin	3 9.7%	3 10%	4 13.3%	10 11%
Metformin dose Number of participants (%) (participants) [Number]
>=1500 mg/day	27 87.1%	28 93.3%	27 90%	82 90.1%
<1500 mg/day	4 12.9%	2 6.7%	3 10%	9 9.9%
Other Abnormalities, Yes or No (participants) [Number]
Yes	8 25.8%	6 20%	3 10%	17 18.7%
No	23 74.2%	24 80%	27 90%	74 81.3%
Active proliferative retinopathy, Yes or No (participants) [Number]
Yes	0 0%	0 0%	0 0%	0 0%
No	31 100%	30 100%	30 100%	91 100%
OAD use evaluated at screening (participants) [Number]
Alpha Glucosidase Inhibitors	2 6.5%	3 10%	4 13.3%	9 9.9%
Biguanides	31 100%	30 100%	30 100%	91 100%
Blood Glucose Lowering Drugs, Excl. Insulins	2 6.5%	3 10%	3 10%	8 8.8%
Combinations Of Oral Blood Glucose Lowering Drugs	0 0%	0 0%	1 3.3%	1 1.1%
Dipeptidyl Peptidase 4 (Dpp-4) Inhibitors	7 22.6%	6 20%	12 40%	25 27.5%
Other Blood Glucose Lowering Drugs, Excl. Insulins	0 0%	1 3.3%	2 6.7%	3 3.3%
Sulfonylureas	22 71%	23 76.7%	25 83.3%	70 76.9%
Thiazolidinediones	2 6.5%	2 6.7%	6 20%	10 11%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c at 24 Weeks (Part 1)
Description	The primary endpoint is change from baseline in HbA1c after 24 weeks of randomized treatment.
Time Frame	Week 0, Week 24

Outcome Measure Data

Analysis Population Description

The analysis of this efficacy endpoint was based on the full analysis set (FAS). FAS included all randomized subjects in Part 1. The statistical evaluation of the FAS was to follow the intention-to-treat (ITT) principle and subjects contributed to the evaluation 'as randomized'.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	Strength of each tablet is 15mg Insulin Tregopil: Drug: Insulin Tregopil (IN-105) Mode of Administration: To be administered orally 10 ± 2 minutes prior to each major meal (breakfast, lunch and dinner) starting at the Randomization visit.	Strength of each tablet is 15mg Insulin Tregopil: Drug: Insulin Tregopil (IN-105) Mode of Administration: To be administered orally 10 ± 2 minutes prior to each major meal (breakfast, lunch and dinner) starting at the Randomization visit.	Pre-filled pen: 100 U/L Insulin Aspart: Drug: Insulin Aspart Mode of Administration: To be administered within 5 minutes prior to each major meal (breakfast, lunch and dinner) starting at the Randomization visit
Measure Participants	31	30	30
Baseline (Week 0)	8.23 (0.577)	8.10 (0.670)	8.07 (0.697)
Week 24	8.38 (1.139)	8.21 (0.969)	7.29 (0.788)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Tregopil (IN-105) - 45mg, Insulin Aspart
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Change from baseline in HbA1c at 24 weeks of treatment, was analyzed using mixed model for repeated measures (MMRM) where all available post-baseline HbA1c measurements obtained up to Week 24 was entered as the dependent variables; visit and treatment were included as fixed factors, with Baseline HbA1c and stratification factor variables as covariates. Furthermore, the interaction terms of visit by treatment, visit by stratification factors and visit by Baseline HbA1c were included in the model.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.502 to 1.470
	Parameter Dispersion	Type: Value:
	Estimation Comments	Insulin Tregopil 45 mg - Insulin Aspart

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Tregopil (IN-105) - 30mg, Insulin Aspart
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non inferiority margin is 0.4%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.414 to 1.370
	Parameter Dispersion	Type: Value:
	Estimation Comments	Insulin Tregopil 30mg - Insulin Aspart

2. Secondary Outcome

Title	Change From Baseline in HbA1c at Week 12 (Part 1)
Description	This secondary outcome is the change from baseline in HbA1c after 12 weeks of randomized treatment. For this endpoint baseline (Week 0) and Week 12 have been presented.
Time Frame	Week 0, Week 12

Outcome Measure Data

Analysis Population Description

This endpoint was summarized using ITT analysis set in Part I. ITT set included all randomized subjects. At Week 12, data from available participants are summarized.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	31	30	30
Baseline (Week 0)	8.23 (0.577)	8.10 (0.670)	8.07 (0.697)
Week 12	8.04 (0.940)	8.01 (0.898)	7.18 (0.810)
Change from Baseline	-0.17 (0.913)	-0.07 (0.866)	-0.88 (0.850)

3. Secondary Outcome

Title	Participants Achieving HbA1c < 7% (Part 1)
Description	Number of participants achieving HbA1c < 7% at Week 12 and Week 24.
Time Frame	Week 12, Week 24

Outcome Measure Data

Analysis Population Description

This endpoint was summarized using intention-to-treat (ITT) analysis set. ITT set included all randomized participants. At Week 12 and Week 24, data from available participants are summarized.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	31	30	30
Week 12	4 12.9%	3 10%	13 43.3%
Week 24	2 6.5%	2 6.7%	10 33.3%

4. Secondary Outcome

Title	Percentage of Participants With Hypoglycemia Events During 24-week Treatment Period (Part 1)
Description	A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤ 70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)]
Time Frame	Week 0 through Week 24

Outcome Measure Data

Analysis Population Description

This endpoint was summarized using safety analysis set in Part I. Safety analysis set included patients who were randomized and took at least 1 dose of the study drug. Patients in the safety analysis set contributed to the evaluation 'as treated'.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	31	30	30
Count of Participants [Participants]	26 83.9%	26 86.7%	25 83.3%

5. Secondary Outcome

Title	Weight (Kgs) (Part 1)
Description	Change from Baseline in weight (kgs) to 24 weeks
Time Frame	Week 0 and Week 24

Outcome Measure Data

Analysis Population Description

This endpoint was summarized using completed participants at Week 24 and all randomised participants at Week 0 in Part I. Change from baseline was summarised using completed participants.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	31	30	30
Baseline (Week 0)	68.54 (11.559)	68.88 (9.040)	67.76 (9.628)
Week24	68.98 (11.837)	70.15 (8.915)	68.47 (9.761)
Change from Baseline	0.93 (1.212)	0.30 (1.955)	0.66 (1.807)

6. Secondary Outcome

Title	Lipid Profile (Part 1)
Description	Change from Baseline in lipid profile (triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol) to 24 weeks
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

This was planned for part 2 of the study. As part-2 of the study was discontinued, this is not applicable.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	0	0	0

7. Secondary Outcome

Title	Post-prandial Glucose (PPG) Excursion (Part 1)
Description	Change from Baseline in the mean 60, 90, 120 minutes PPG excursions assessed from standardized test meal at Week 24.
Time Frame	Week 0, Week 24

Outcome Measure Data

Analysis Population Description

This endpoint was summarized using the intention-to-treat (ITT) analysis set from Part I. ITT set included all randomized participants. At Week 24, data from available participants are summarized.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	31	30	30
Week 0, 60 min	79.5 (45.53)	98.3 (41.94)	74.4 (42.85)
Week 0, 90 min	92.4 (47.94)	106.4 (35.39)	90.8 (35.35)
Week 0, 120 min	100.9 (58.18)	113.5 (53.45)	93.7 (41.20)
Week 24, 60 min	35.8 (44.26)	32.7 (45.13)	55.1 (34.57)
Week 24, 90 min	53.8 (45.38)	47.2 (44.84)	66.3 (36.13)
Week 24, 120 min	64.1 (51.87)	50.2 (44.23)	65.5 (34.58)

8. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (Part 1)
Description	Includes participants who have experienced at least one treatment emergent adverse events over 24 weeks
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

This endpoint was summarized using Treatment Emergent Adverse Events - Safety Analysis Set (Part I).

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	31	30	30
Count of Participants [Participants]	5 16.1%	6 20%	4 13.3%

9. Secondary Outcome

Title	Anti-drug Antibody Levels
Description	Incidence and change from baseline in the relative levels of anti-drug antibody levels over 24 weeks
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

This was planned for part 2 of the study. As part-2 of the study was discontinued, this is not applicable.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	0	0	0

10. Secondary Outcome

Title	CGM
Description	Area under the glucose curve below 70 mg/dL derived from CGM, applicable for only part II study
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

This was planned for part 2 of the study. As part-2 of the study was discontinued, this is not applicable.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	0	0	0

11. Other Pre-specified Outcome

Title	Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24
Description	Number of participants achieving HbA1c < 7% at Week 12 and Week 24 without reported clinically significant or severe hypoglycemic events between end of Week 8 and Week 24.
Time Frame	Week 12, Week 24

Outcome Measure Data

Analysis Population Description

This endpoint was summarized using intention-to-treat (ITT) analysis set in Part I. ITT set included all randomized participants. At Week 12 and Week 24, data from available participant are summarized.

Arm/Group Title	Insulin Tregopil (IN-105) - 45mg	Insulin Tregopil (IN-105) - 30mg	Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.	At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
Measure Participants	31	30	30
Week 12	4 12.9%	3 10%	11 36.7%
Week 24	1 3.2%	3 10%	7 23.3%

Adverse Events

Time Frame	From the date on or after first day of exposure to randomized treatment until the last day of randomized treatment, an average of 24 weeks.
Adverse Event Reporting Description	Safety analysis set was used for the assessment of safety including AEs. The safety analysis set included all subjects who received at least one dose of test product.
Arm/Group Title	Insulin Tregopil (IN-105) - 45mg		Insulin Tregopil (IN-105) - 30mg		Insulin Aspart
Arm/Group Description	At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.		SAt randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.		At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose
All Cause Mortality
	Insulin Tregopil (IN-105) - 45mg		Insulin Tregopil (IN-105) - 30mg		Insulin Aspart
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Insulin Tregopil (IN-105) - 45mg		Insulin Tregopil (IN-105) - 30mg		Insulin Aspart
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Insulin Tregopil (IN-105) - 45mg		Insulin Tregopil (IN-105) - 30mg		Insulin Aspart
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/31 (16.1%)		5/30 (16.7%)		4/30 (13.3%)
Gastrointestinal disorders
Gastritis	1/31 (3.2%)	1	1/30 (3.3%)	1	0/30 (0%)	0
Nausea	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
General disorders
Pyrexia	1/31 (3.2%)	2	1/30 (3.3%)	1	0/30 (0%)	0
Pain	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Infections and infestations
Urinary tract infection	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Dysentery	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Upper respiratory tract infection	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Urinary tract infection viral	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Injury, poisoning and procedural complications
Fall	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Vulval laceration	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Investigations
Blood creatinine increased	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Haemoglobin decreased	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Hepatic enzyme increased	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Weight increased	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Vitamin D deficiency	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/31 (3.2%)	2	0/30 (0%)	0	0/30 (0%)	0
Back pain	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Nervous system disorders
Dizziness	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Hypoaesthesia	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Lethargy	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Paraesthesia	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Vascular disorders	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Hypertension	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.