Mylan Insulin Glargine Study

• Sponsor: Mylan Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03376789
• Collaborator: Mylan GmbH (Industry)
• Enrollment: 219
• Locations: 38
• Arms: 2
• Actual Duration (Months): 13.4
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The aim of this study is to demonstrate similar efficacy and safety between MYL-1501D products produced from two manufacturing processes (Process V and Process VI) in combination with insulin lispro in patients with type 1 diabetes mellitus (T1DM).

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: MYL-1501D product using manufacture process V; Drug: MYL-1501D product using manufacture process VI	Phase 3

Detailed Description

This is a multicenter, double-blind, randomized, parallel-group Phase 3 study in subjects with type 1 diabetes mellitus (T1DM) comparing the efficacy, immunogenicity, and safety of MYL-1501D products from 2 manufacturing processes (Process V and Process VI). After a 2-week screening period, all subjects will be titrated on Lantus® during a 4-week run-in period and shifted from their current mealtime insulin to insulin lispro (Humalog®). Subjects will then be randomized (stratified by time of administration of glargine [morning and evening]) to 1 of 2 groups:

• MYL-1501D product from Process V

• MYL-1501D product from Process VI Treatment with MYL-1501D is for 18 weeks. A follow-up visit is scheduled 2 weeks after last dose of MYL 1501D.

Study Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multi-center, Double-Blind, Parallel-Group Clinical Study Comparing the Efficacy and Safety of MYL-1501D Produced by Two Manufacturing Processes in Type 1 Diabetes Mellitus Patients
• Actual Study Start Date: Nov 29, 2017
• Actual Primary Completion Date: Sep 25, 2018
• Actual Study Completion Date: Jan 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: MYL-1501D (Process V Product) MYL-1501D (Process V Product)	Drug: MYL-1501D product using manufacture process V; MYL-1501D product using manufacture process V
Active Comparator: MYL-1501D (Process VI Product) MYL-1501D (Process VI Product)	Drug: MYL-1501D product using manufacture process VI; MYL-1501D product using manufacture process VI

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c [Baseline to Week 18]

   Change in HbA1c from baseline

Secondary Outcome Measures

1. Change in FPG [Baseline to Week 18]

   Change in fasting plasma glucose from baseline

2. Change in Insulin Dose [Baseline to Week 18]

   Change in daily total insulin dose per unit body weight (U/kg) from baseline

3. Change in 8-point SMBG [Baseline to Week 18]

   Change in 8-point self-monitored blood glucose (SMBG) daily average

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written and signed informed consent needs to be provided by subjects or their legal representatives before starting any protocol-specific procedures.

2. Male and female subjects between the ages of 18 to 65 years, both ages inclusive.

3. Subjects with an established diagnosis of T1DM per ADA 2017 criteria who also fulfil the following criteria:

4. Initiation of insulin treatment within 6 months of T1DM diagnosis

5. Treatment with basal-bolus insulin therapy for at least 1 year before screening

6. Fasting plasma C-peptide <0.3 nmol/L at screening

7. Subject has been on once daily Lantus® at stable dose (±15% variation in dose) for at least 3 months at screening

8. Body mass index (BMI) of 18.5 to 35 kg/m2 at screening (both values inclusive).

9. Stable weight, with no more than 5 kg gain or loss in the 3 months prior to screening, this information will be collected by subject interview during medical history.

10. Glycosylated hemoglobin (HbA1c) ≤ 9.5% at screening.

11. Hemoglobin ≥9.0 g/dL at screening.

12. Subject has the capability of communicating appropriately with the investigator.

13. Subject is able and willing to comply with the requirements of the study protocol including the 8-point self-monitored blood glucose (SMBG), completion of subject diary records and following a recommended diet and exercise plan for the entire duration of the study.

14. Female subjects of childbearing potential who are willing to use oral contraception or two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through study completion.

15. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

16. Postmenopausal females must have had no regular menstrual bleeding for at least 1 year prior to screening.

17. Female subjects who report surgical sterilization must have had the procedure at least 6 months prior to screening.

18. All female subjects of childbearing potential must have negative pregnancy test results at screening and at clinic visits, as per the SCHEDULE OF ACTIVITIES (SOA).

19. If female subjects have male partners who have undergone vasectomy, the vasectomy must have occurred more than 6 months prior to screening

Exclusion Criteria:

1. History or presence of a medical condition or disease that in the investigator's opinion would place the subject at an unacceptable risk from study participation.

2. History of hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analogue preparations used in the study, OR history of significant allergic drug reactions.

3. History of use of animal insulin within the last 3 years or use of approved biosimilar insulin glargine at any time prior to study entry, except for subject who previously participated in MYL-1501D studies and were compliant with the study protocols.

4. History of use of a regular immunomodulator therapy in the 1 year prior to screening.

5. History of autoimmune disorders other than T1DM or insufficiently treated autoimmune thyroid disorders judged clinically relevant by the investigator (recorded while collecting subject history).

6. History of ≥1 episodes of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months prior to screening.

7. History of clinically significant acute bacterial, viral or fungal systemic infections in the last 4 weeks prior to screening (recorded while collecting subject history).

8. Any clinically significant abnormality in electrocardiogram (ECG) or safety laboratory tests (LFT, RFT, hematology or any other laboratory deemed clinically relevant by the investigator) conducted at screening and considered by the investigator to make the subject ineligible for the study.

9. Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HbSAg) or hepatitis C antibodies (HCVAb) at screening.

10. History of drug or alcohol dependence or abuse during the 1 year prior to screening.

11. Receipt of another investigational drug in the 3 months prior to screening (or as per local regulations), or if the screening visit is within 5 half-lives of another investigational drug received (whichever is longer), or scheduled to receive another investigational drug during the current study period.

12. Subjects with the following secondary complications of diabetes:

13. Active proliferative retinopathy as confirmed by a dilated ophthalmoscopy examination / retinal photography (performed by a person legally authorized to do so) within the 6 months prior to screening.

14. Clinical nephrotic syndrome or diabetic nephropathy with a serum creatinine level

1.5 times of upper limit of reference range at screening

1. History of severe form of neuropathy or cardiac autonomic neuropathy, recorded while collecting subject history. Subject's with mild or moderate forms of neuropathy will be allowed.

2. Subjects with a history of limb amputation as a complication of diabetes (at any time), or any vascular procedure during the 1 year prior to screening.

3. History of diabetic foot or diabetic ulcers in the 1 year prior to screening.

4. Any elective surgery requiring hospitalization planned during the study period.

5. Clinically significant major organ disorder at the time of screening including:

6. Uncontrolled hypertension, defined as stage 2 hypertension by Joint National Committee VII (even if therapy is ongoing, blood pressure ≥160 mm Hg systolic or ≥100 mm Hg diastolic).

7. Uncontrolled hyperlipidemia (even if therapy is ongoing, LDL >160 mg/dL or triglycerides >500 mg/dL).

8. Uncontrolled hyperthyroidism or hypothyroidism (subjects can be included if these conditions are controlled with thyroid hormones or anti-thyroid drugs).

9. Impaired hepatic function (alanine transaminase [ALT] or aspartate transaminase [AST] value >2 times the upper limit of the reference range and/or serum bilirubin 1.5 times the upper limit of the reference range at the screening visit). Subjects with evidence of Gilberts disease may be included in the study if they have total bilirubin of <3 mg/dL with indirect bilirubin contributing to

80% of the total bilirubin.

1. History of a significant medical condition, such as:

2. Clinically significant cardiac disease like unstable angina, myocardial infarction, grade 3 or 4 congestive heart failure (CHF) according to New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, and pulmonary hypertension; during the year prior to screening.

3. Stroke or transient ischemic attack (TIA) in the 6 months before screening.

4. Subjects with major depressive illness in the last 3 years (those who have well-controlled depression for 3 months on a stable dose of antidepressants, with no major depressive episodes in the last 3 years, can be included, even if they are on medication), subjects with history of other severe psychiatric diseases (manic depressive psychosis [MDP], schizophrenia), which in the opinion of the investigator precludes the subject from participating in the study (recorded while collecting subject history).

5. History of hematological disorders that can affect the reliability of HbA1c estimation (hemoglobinopathies, hemolytic anemia, sickle cell anemia, etc.).

6. Subjects using the following in the 3 months prior to screening:

7. Insulin pump therapy

8. Any anti-diabetic drugs other than the study insulins allowed by the protocol.

9. Moderate insulin resistance, defined as requiring insulin of ≥1.5 U/IU/kg/day.

10. Subjects who have received ≥14 consecutive days of glucocorticoid therapy by oral, intravenous, inhaled or other routes that produce systemic effects within the past 1 year, or who have received steroids by any route (except intra-nasal, intra-ocular, and topical) within the 4 weeks immediately preceding screening.

11. Subjects diagnosed as having cancer (subjects with history of basal cell carcinoma, carcinoma in situ or squamous cell cancer of skin, or in remission >5 years, will be allowed).

12. Subjects who have donated blood or plasma in the 1 month prior to screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mylan Investigator Site	Fresno	California	United States	93720
2	Mylan Investigator Site	Greenbrae	California	United States	94904
3	Mylan Investigator Site	Huntington Beach	California	United States	92648
4	Mylan Investigator Site	La Mesa	California	United States	91942
5	Mylan Investigator Site	Los Gatos	California	United States	95032
6	Mylan Investigator Site	Mission Hills	California	United States	91345
7	Mylan Investigator Site	Montclair	California	United States	91763
8	Mylan Investigator Site	Northridge	California	United States	91324
9	Mylan Investigator Site	Oakland	California	United States	94607
10	Mylan Investigator Site	Santa Monica	California	United States	90404
11	Mylan Investigator Site	Tarzana	California	United States	91356
12	Mylan Investigator Site	Tustin	California	United States	92780
13	Mylan Investigator Site	Walnut Creek	California	United States	94598
14	Mylan Investigator Site	Denver	Colorado	United States	80246
15	Mylan Investigator Site	Bradenton	Florida	United States	34201
16	Mylan Investigator Site	Fort Lauderdale	Florida	United States	33312
17	Mylan Investigator Site	Fort Myers	Florida	United States	33912
18	Mylan Investigator Site	Hialeah	Florida	United States	33012
19	Mylan Investigator Site	Maitland	Florida	United States	32751
20	Mylan Investigator Site	Miami	Florida	United States	33126
21	Mylan Investigator Site	Miami	Florida	United States	33156
22	Mylan Investigator Site	Miami	Florida	United States	33175
23	Mylan Investigator Site	New Port Richey	Florida	United States	34652
24	Mylan Investigator Site	Palm Harbor	Florida	United States	34684
25	Mylan Investigator Site	Saint Petersburg	Florida	United States	33709
26	Mylan Investigator Site	Spring Hill	Florida	United States	34609
27	Mylan Investigator Site	Tampa	Florida	United States	33634
28	Mylan Investigator Site	West Palm Beach	Florida	United States	33401
29	Mylan Investigator Site	Atlanta	Georgia	United States	30318
30	Mylan Investigator Site	Columbus	Georgia	United States	31904
31	Mylan Investigator Site	Lawrenceville	Georgia	United States	30045
32	Mylan Investigator Site	Roswell	Georgia	United States	30076
33	Mylan Investigator Site	Idaho Falls	Idaho	United States	83404
34	Mylan Investigator Site	Meridian	Idaho	United States	83642
35	Mylan Investigator Site	Springfield	Illinois	United States	62701
36	Mylan Investigator Site	Council Bluffs	Iowa	United States	51501
37	Mylan Investigator Site	Austin	Texas	United States	78731
38	Mylan Investigator Site	Dallas	Texas	United States	75231

Sponsors and Collaborators

• Mylan Inc.
• Mylan GmbH

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 11, 2018
• Statistical Analysis Plan - Oct 18, 2018

More Information

Publications

None provided.

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT03376789
• Other Study ID Numbers: MYL-1501D-3004
• First Posted: Dec 18, 2017
• Last Update Posted: Mar 3, 2022
• Last Verified: Mar 1, 2022

• 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
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; MYL-1501D

Study Results

Participant Flow

Arm/Group Title	MYL-1501D (Process V Product)	MYL-1501D (Process VI Product)
Arm/Group Description	MYL-1501D (Process V Product) MYL-1501D: Process V or Process VI	MYL-1501D (Process VI Product) MYL-1501D: Process V or Process VI
Period Title: Overall Study
STARTED	108	111
COMPLETED	103	102
NOT COMPLETED	5	9

Baseline Characteristics

Arm/Group Title	MYL-1501D (Process V Product)	MYL-1501D (Process VI Product)	Total
Arm/Group Description	MYL-1501D (Process V Product) MYL-1501D: Process V or Process VI	MYL-1501D (Process VI Product) MYL-1501D: Process V or Process VI	Total of all reporting groups
Overall Participants	108	111	219
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.7 (11.46)	42.8 (12.14)	42.8 (11.78)
Sex: Female, Male (Count of Participants)
Female	36 33.3%	35 31.5%	71 32.4%
Male	72 66.7%	76 68.5%	148 67.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 6.5%	11 9.9%	18 8.2%
Not Hispanic or Latino	98 90.7%	98 88.3%	196 89.5%
Unknown or Not Reported	3 2.8%	2 1.8%	5 2.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.9%	1 0.9%	2 0.9%
Asian	6 5.6%	2 1.8%	8 3.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 5.6%	5 4.5%	11 5%
White	95 88%	103 92.8%	198 90.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Screening Weight (kg) (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	83.58 (16.137)	82.42 (14.782)	82.99 (15.441)
Screening BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.37 (3.726)	27.29 (3.927)	27.33 (3.821)
Duration of diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.321 (13.2876)	21.736 (13.3418)	22.025 (13.2878)
Time of glargine administration (Count of Participants)
Morning	32 29.6%	37 33.3%	69 31.5%
Evening	76 70.4%	74 66.7%	150 68.5%
Baseline FPG (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	8.793 (3.9095)	9.065 (3.7223)	8.931 (3.8094)
Baseline HbA1c (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	7.281 (0.8759)	7.371 (0.8681)	7.327 (0.8711)
Insulin use prior to screening (Count of Participants)
Yes	108 100%	111 100%	219 100%
No	0 0%	0 0%	0 0%
Fasting C-peptide (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	0.041 (0.0430)	0.039 (0.0533)	0.040 (0.0484)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c
Description	Change in HbA1c from baseline
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MYL-1501D (Process V Product)	MYL-1501D (Process VI Product)
Arm/Group Description	MYL-1501D (Process V Product) MYL-1501D: Process V or Process VI	MYL-1501D (Process VI Product) MYL-1501D: Process V or Process VI
Measure Participants	108	111
Least Squares Mean (Standard Error) [percentage of change]	0.18 (0.055)	0.15 (0.053)

2. Secondary Outcome

Title	Change in FPG
Description	Change in fasting plasma glucose from baseline
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MYL-1501D (Process V Product)	MYL-1501D (Process VI Product)
Arm/Group Description	MYL-1501D (Process V Product) MYL-1501D: Process V or Process VI	MYL-1501D (Process VI Product) MYL-1501D: Process V or Process VI
Measure Participants	108	111
Mean (Standard Deviation) [mmol/L]	0.64 (5.754)	0.01 (4.767)

3. Secondary Outcome

Title	Change in Insulin Dose
Description	Change in daily total insulin dose per unit body weight (U/kg) from baseline
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MYL-1501D (Process V Product)	MYL-1501D (Process VI Product)
Arm/Group Description	MYL-1501D (Process V Product) MYL-1501D: Process V or Process VI	MYL-1501D (Process VI Product) MYL-1501D: Process V or Process VI
Measure Participants	108	111
Mean (Standard Deviation) [Units per kilogram]	-0.004 (0.1039)	0.007 (0.0884)

4. Secondary Outcome

Title	Change in 8-point SMBG
Description	Change in 8-point self-monitored blood glucose (SMBG) daily average
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MYL-1501D (Process V Product)	MYL-1501D (Process VI Product)
Arm/Group Description	MYL-1501D (Process V Product) MYL-1501D: Process V or Process VI	MYL-1501D (Process VI Product) MYL-1501D: Process V or Process VI
Measure Participants	108	111
Mean (Standard Deviation) [mmol/L]	0.10 (1.317)	0.11 (1.743)

Adverse Events

Time Frame	Adverse events were collected from time of signing Informed Consent through completion of the Follow-up visit, an average of 26 weeks. All safety analyses were carried out using the Safety population, which was defined as all subjects who were randomized and received ≥ 1 dose of IP.
Arm/Group Title	MYL-1501D (Process V Product)		MYL-1501D (Process VI Product)
Arm/Group Description	MYL-1501D (Process V Product) MYL-1501D: Process V or Process VI		MYL-1501D (Process VI Product) MYL-1501D: Process V or Process VI
All Cause Mortality
	MYL-1501D (Process V Product)		MYL-1501D (Process VI Product)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/108 (0%)		0/110 (0%)
Serious Adverse Events
	MYL-1501D (Process V Product)		MYL-1501D (Process VI Product)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/108 (2.8%)		7/110 (6.4%)
Immune system disorders
Food allergy	0/108 (0%)	0	1/110 (0.9%)	1
Injury, poisoning and procedural complications
Laceration	0/108 (0%)	0	1/110 (0.9%)	1
Metabolism and nutrition disorders
Hypoglycaemia	3/108 (2.8%)	4	4/110 (3.6%)	4
Diabetic ketoacidosis	0/108 (0%)	0	1/110 (0.9%)	1
Other (Not Including Serious) Adverse Events
	MYL-1501D (Process V Product)		MYL-1501D (Process VI Product)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/108 (41.7%)		46/110 (41.8%)
Cardiac disorders
Bundle branch block right	1/108 (0.9%)	1	0/110 (0%)	0
Left atrial enlargement	1/108 (0.9%)	1	0/110 (0%)	0
Ear and labyrinth disorders
Cerumen impaction	1/108 (0.9%)	1	0/110 (0%)	0
Endocrine disorders
Hypothyroidism	0/108 (0%)	0	1/110 (0.9%)	1
Eye disorders
Vitreous haemorrhage	0/108 (0%)	0	1/110 (0.9%)	1
Gastrointestinal disorders
Diarrhoea	4/108 (3.7%)	5	2/110 (1.8%)	2
Nausea	1/108 (0.9%)	5	5/110 (4.5%)	6
Vomiting	1/108 (0.9%)	5	5/110 (4.5%)	6
Gastrooesophagael reflux disease	0/108 (0%)	0	2/110 (1.8%)	2
Abdominal pain	0/108 (0%)	0	2/110 (1.8%)	2
Abdominal pain upper	0/108 (0%)	0	2/110 (1.8%)	2
Constipation	0/108 (0%)	0	1/110 (0.9%)	1
Dyspepsia	0/108 (0%)	0	1/110 (0.9%)	1
Gingival swelling	0/108 (0%)	0	1/110 (0.9%)	1
General disorders
Chills	1/108 (0.9%)	1	0/110 (0%)	0
Injection site haemorrhage	0/108 (0%)	0	1/110 (0.9%)	1
Injection site rash	0/108 (0%)	0	1/110 (0.9%)	1
Non-cardiac chest pain	1/108 (0.9%)	1	0/110 (0%)	0
Systemic inflammatory response syndrome	0/108 (0%)	0	1/110 (0.9%)	1
Immune system disorders
Food allergy	0/108 (0%)	0	1/110 (0.9%)	1
Seasonal allergy	1/108 (0.9%)	1	0/110 (0%)	0
Infections and infestations
Upper respiratory tract infection	7/108 (6.5%)	7	3/110 (2.7%)	3
Nasopharyngitis	4/108 (3.7%)	4	4/110 (3.6%)	4
Gastroenteritis	4/108 (3.7%)	5	3/110 (2.7%)	3
Gastroenteritis viral	0/108 (0%)	0	4/110 (3.6%)	4
Respiratory tract infection	1/108 (0.9%)	1	1/110 (0.9%)	1
Sinusitis	1/108 (0.9%)	1	1/110 (0.9%)	1
Urinary tract infection	2/108 (1.9%)	2	0/110 (0%)	0
Bronchitis	0/108 (0%)	0	1/110 (0.9%)	1
Cellulitis	0/108 (0%)	0	1/110 (0.9%)	1
Diverticulitis	1/108 (0.9%)	1	0/110 (0%)	0
Ear infection	0/108 (0%)	0	1/110 (0.9%)	1
Gastrointestinal bacterial infection	0/108 (0%)	0	1/110 (0.9%)	1
Genital herpes simplex	0/108 (0%)	0	1/110 (0.9%)	1
Injection site infection	0/108 (0%)	0	1/110 (0.9%)	1
Onychomycosis	0/108 (0%)	0	1/110 (0.9%)	1
Oral candidiasis	0/108 (0%)	0	1/110 (0.9%)	1
Oral herpes	1/108 (0.9%)	1	0/110 (0%)	0
Pharyngitis	0/108 (0%)	0	1/110 (0.9%)	1
Pyuria	0/108 (0%)	0	1/110 (0.9%)	1
Respiratory tract infection viral	0/108 (0%)	0	1/110 (0.9%)	1
Root canal infection	1/108 (0.9%)	1	0/110 (0%)	0
Tooth infection	1/108 (0.9%)	1	0/110 (0%)	0
Viral respiratory tract infection	1/108 (0.9%)	1	0/110 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	1/108 (0.9%)	1	1/110 (0.9%)	1
Foot fracture	1/108 (0.9%)	1	1/110 (0.9%)	1
Thermal burn	2/108 (1.9%)	2	0/110 (0%)	0
Contusion	0/108 (0%)	0	1/110 (0.9%)	1
Hand fracture	0/108 (0%)	0	1/110 (0.9%)	1
Joint injury	1/108 (0.9%)	1	0/110 (0%)	0
Laceration	0/108 (0%)	0	1/110 (0.9%)	1
Ligament sprain	1/108 (0.9%)	1	0/110 (0%)	0
Limb injury	1/108 (0.9%)	1	0/110 (0%)	0
Radius fracture	0/108 (0%)	0	1/110 (0.9%)	1
Skin wound	0/108 (0%)	0	1/110 (0.9%)	1
Tendon rupture	0/108 (0%)	0	1/110 (0.9%)	1
Wound	1/108 (0.9%)	1	0/110 (0%)	0
Investigations
Alanine aminotransferase increased	1/108 (0.9%)	1	1/110 (0.9%)	1
Aspartate aminotransferase increased	1/108 (0.9%)	1	1/110 (0.9%)	1
Weight increased	1/108 (0.9%)	1	1/110 (0.9%)	1
Blood creatinine increased	0/108 (0%)	0	1/110 (0.9%)	1
Blood glucose increased	0/108 (0%)	0	1/110 (0.9%)	1
Blood potassium increased	0/108 (0%)	0	1/110 (0.9%)	1
Blood urea increased	0/108 (0%)	0	1/110 (0.9%)	1
Weight decreased	1/108 (0.9%)	1	0/110 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	3/108 (2.8%)	4	4/110 (3.6%)	4
Hyperlipidaemia	0/108 (0%)	0	2/110 (1.8%)	2
Ketosis	1/108 (0.9%)	1	1/110 (0.9%)	1
Diabetic ketoacidosis	0/108 (0%)	0	1/110 (0.9%)	1
Dyslipidaemia	1/108 (0.9%)	1	0/110 (0%)	0
Hyperglycaemia	0/108 (0%)	0	1/110 (0.9%)	1
Hyperkalemia	0/108 (0%)	0	1/110 (0.9%)	1
Increased appetite	0/108 (0%)	0	1/110 (0.9%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/108 (0.9%)	1	2/110 (1.8%)	2
Pain in extremity	1/108 (0.9%)	1	2/110 (1.8%)	2
Tendonitis	1/108 (0.9%)	1	2/110 (1.8%)	2
Arthralgia	2/108 (1.9%)	2	0/110 (0%)	0
Myalgia	0/108 (0%)	0	2/110 (1.8%)	2
Flank pain	1/108 (0.9%)	1	0/110 (0%)	0
Muscle spasms	1/108 (0.9%)	1	0/110 (0%)	0
Nervous system disorders
Headache	1/108 (0.9%)	1	2/110 (1.8%)	2
Dizziness	0/108 (0%)	0	2/110 (1.8%)	2
Migraine	2/108 (1.9%)	2	0/110 (0%)	0
Sinus headache	1/108 (0.9%)	1	0/110 (0%)	0
Psychiatric disorders
Depression	0/108 (0%)	0	1/110 (0.9%)	1
Insomnia	1/108 (0.9%)	1	0/110 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/108 (0%)	0	1/110 (0.9%)	1
Dysuria	0/108 (0%)	0	1/110 (0.9%)	1
Renal failure	1/108 (0.9%)	1	0/110 (0%)	0
Reproductive system and breast disorders
Dysmenorrhoea	0/108 (0%)	0	1/110 (0.9%)	1
Ovarian cyst	0/108 (0%)	0	1/110 (0.9%)	1
Pelvic pain	1/108 (0.9%)	1	0/110 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal congestion	2/108 (1.9%)	2	0/110 (0%)	0
Cough	0/108 (0%)	0	1/110 (0.9%)	1
Dyspnoea	0/108 (0%)	0	1/110 (0.9%)	1
Paranasal sinus discomfort	0/108 (0%)	0	1/110 (0.9%)	1
Rhinitis allergic	1/108 (0.9%)	1	0/110 (0%)	0
Sinus congestion	0/108 (0%)	0	1/110 (0.9%)	1
Sneezing	1/108 (0.9%)	1	0/110 (0%)	0
Skin and subcutaneous tissue disorders
Rash	2/108 (1.9%)	2	0/110 (0%)	0
Actinic keratosis	1/108 (0.9%)	1	0/110 (0%)	0
Dermatitis contact	0/108 (0%)	0	1/110 (0.9%)	1
Pain of skin	0/108 (0%)	0	1/110 (0.9%)	1
Pruritis	0/108 (0%)	0	1/110 (0.9%)	1
Surgical and medical procedures
Vasectomy	1/108 (0.9%)	1	0/110 (0%)	0
Vascular disorders
Hypertension	0/108 (0%)	0	2/110 (1.8%)	2
Hypotension	0/108 (0%)	0	1/110 (0.9%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.