Safety Evaluation of the Hybrid Closed Loop (HCL) System in Pediatric Subjects With Type 1 Diabetes

• Sponsor: Medtronic Diabetes (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02660827
• Collaborator: (none)
• Enrollment: 151
• Locations: 11
• Arm: 1
• Actual Duration (Months): 57.5
• Patients Per Site: 13.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is a single-arm, multi-center, Home and Hotel Clinical Investigation in pediatric subjects with type 1 diabetes on insulin pump therapy. The purpose of this study is to demonstrate that the closed loop algorithm is safe as part of the overall system, and to assess the PLGM feature in 7-13 years old subjects.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Device: Insulin Pump	N/A

Detailed Description

The study will proceed as follows:

Run-in Period - General:

A total of up to 200 subjects (age 2-13) will be enrolled at up to 15 investigational centers (14 in the US, 1 EMEA) in order to reach 120 subjects who will complete the HCL study.

Study Period - At Home:

Following the two week run-in period using the Study Pump (670G), all subjects (age 2-13) will participate in a 3-month study period.

Study Period - Hotel Study Subjects (age 7-13) will participate in a Hotel study (6 days, 5 nights), with the remainder of the study period to be spent at home. Subjects 2-6 years of age are not required to participate in a hotel study. Instead, they will participate in an out-of-home study for 5 consecutive days, 4-6 hours per day.

Continued Access Program Subjects will be given the opportunity to extend use of their study devices for a period of up to 3 years . If subjects choose to participate in the continuation period, they will retain the study devices at the end of study period visit or receive them back in the event they have been returned to study staff already.

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety Evaluation of the Hybrid Closed Loop (HCL) System in Pediatric Subjects With Type 1 Diabetes
• Actual Study Start Date: Apr 18, 2016
• Actual Primary Completion Date: Nov 28, 2018
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hybrid closed loop All subjects will be wearing the MMT-670G insulin pump, using it with the closed loop algorithm	Device: Insulin Pump; Closed Loop Algorithm; Other Names: MMT-670G

Outcome Measures

Primary Outcome Measures

1. Age 2-13 Years Old Subjects Change in A1C [Baseline and end of 3-month study period]

   Descriptive analysis of change in A1C from baseline to end of 3-month study period

Secondary Outcome Measures

1. Age 2-13 Years Old Subjects Mean Change in % of Time in Euglycemia (70-180 mg/dL) [baseline and 3 months]

   mean change in % of time in Euglycemia (70-180 mg/dL) from baseline to 3 months study period

2. Age 2-13 Years Old Subjects Mean Change in % of Time in Hyperglycemia (> 180 mg/dL) [baseline and 3 months]

   mean change in % of time in hyperglycemia (> 180 mg/dL) from baseline to 3 months study period

3. Age 2-13 Years Old Subjects Mean Change in % of Time in Hypoglycemia (<70 mg/dL) [baseline and 3 months]

   mean change in % of time in hypoglycemia (< 70 mg/dL) from baseline to 3 months study period

4. Age 2-13 Years Old - Number of Severe Hypoglycemic Event [3 months]

   Number of severe hypoglycemic events occurred during 3-month study period.

5. Age 2-13 Years Old - Number of Diabetic Ketoacidosis (DKA) Event [3 months]

   Number of Diabetic Ketoacidosis (DKA) events occurred during 3-month study period.

6. Age 7-13 Years Old Subjects PLGM Performance - Event Rate Without Hypoglycemia at YSI-FST <=65 mg/dL [Up to 12 hours after the start of PLGM period]

   Event rate without Hypoglycemia at YSI-FST <=65 mg/dL among 105 subjects who underwent the PLGM experiments. The event rate without hypoglycemia is the number of experiments without hypoglycemia/total number of experiments and hypoglycemic events are defined based on the occurrence of 2 or more continuous YSI-FST <= 65mg/dL during in-clinic procedures.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 13 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

General Inclusion Criteria

1. Subject is age 2-13 years at time of screening

2. Subject has a clinical diagnosis of type 1 diabetes for 1 year or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis

3. Subject age 2-6 years has a clinical diagnosis of type 1 diabetes for 3 months or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis

Study-specific inclusion criteria

1. Subject must have a minimum daily insulin requirement (Total Daily Dose) of greater than or equal to 8 units

2. Subjects 7-13: Subjects and their parent(s)/guardian(s) are willing to participate in an overnight visit at the end of the run-in period.

3. Subject 7-13 years of age and their parent(s)/guardian(s) are willing to participate in a hotel study for the specified duration of hotel stay.

4. Subject 2-6 years of age and their parent(s)/guardian(s) are willing to participate in an extended visit during the study period to perform Frequent Sample Testing.

5. Subject must have companion 18 years or older who will sleep in the same dwelling place every night during the study period. This requirement may be verified by subject report at screening visit.

6. Subject is willing to perform ≥ 4 finger stick blood glucose measurements daily

7. Subject is willing to perform required sensor calibrations

8. Subject is willing to wear the system continuously throughout the study

9. Subject has a Glycosylated hemoglobin (A1C) value less than 10.0% (as processed by Central Lab) at time of screening visit Note: All HbA1C blood specimens will be sent to and tested by a NGSP certified Central Laboratory. A1C testing must follow National Glycohemoglobin Standardization Program (NGSP) standards.

10. Subject has TSH in the normal range OR if the TSH is out of normal reference range the Free T3 is below or within the lab's reference range and Free T4 is within the normal reference range.

11. Subject 7 -13 years of age has had pump therapy for greater than 6 months prior to screening (with or without CGM experience)

12. Subject 2-6 years of age has had pump therapy for greater than 90 days prior to screening (with or without CGM experience)

13. Subjects and their parent(s)/guardian(s) are willing to upload data from the study pump; must have Internet access and a computer system that meets the requirements for uploading the study pump

14. If subject has celiac disease, it has been adequately treated as determined by the investigator

15. Subjects and their parent(s)/guardian(s) are willing to take one of the following insulins and can financially support the use of either of the 2 insulin preparations throughout the course of the study (i.e. co-payments for insulin with insurance or able to pay full amount)

• Humalog® (insulin lispro injection)

• NovoLog® (insulin aspart)

1. Subjects and their parent(s)/guardian(s)/companions must be able to speak and be literate in English as verified by the investigator

Exclusion Criteria:

1. Subject has a history of 2 or more episodes of severe hypoglycemia, which resulted in any the following during the 6 months prior to screening:

2. Medical assistance (i.e. Paramedics, Emergency Room ( ER) or Hospitalization)

3. Coma

4. Seizures

5. Subject is unable to tolerate tape adhesive in the area of sensor placement

6. Subject has any unresolved adverse skin condition in the area of sensor placement (e.g., psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection)

7. Females who are sexually active and able to conceive will be excluded if they are not using an effective method of contraception and do not agree to continue using an effective method of contraception for the duration of the study as determined by investigator.

8. Subject has a cardiovascular condition which the investigator determines should exclude the subject, i.e. ventricular rhythm disturbance, hypertrophic cardiomyopathy

9. Subject is being treated for hyperthyroidism at time of screening

10. Subject has diagnosis of adrenal insufficiency

11. Subject 7-13 years of age has had DKA in the 6 months prior to screening visit.

12. Subject 2-6 years of age has had DKA in the 3 months prior to screening visit

13. Subject has taken any oral, injectable, or intravenous (IV) glucocorticoids within 8 weeks from time of screening visit, or plans to take any oral, injectable, or IV glucocorticoids during the course of the study

14. Subject is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or investigational study device in the last 2 weeks

15. Subject 7-13 years of age has been hospitalized or has visited the ER in the 6 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes

16. Subject 2-6 years of age has been hospitalized or has visited the ER in the 3 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes

17. Subject is currently abusing illicit drugs

18. Subject is currently abusing marijuana.

19. Subject is currently abusing prescription drugs

20. Subject is currently abusing alcohol

21. Subject is using pramlintide (Symlin), DPP-4 inhibitor, liraglutide (Victoza or other GLP-1 agonists), metformin, canagliflozin (Invokana or other SGLT2 inhibitors) at time of screening

22. Subject has a history of visual impairment which would not allow subject to participate in the study and perform all study procedures safely, as determined by the investigator

23. Subject has elective surgery planned that requires general anesthesia during the course of the study

24. Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening

25. Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation

26. Subject diagnosed with current eating disorder such as anorexia or bulimia

27. Subject has been diagnosed with chronic kidney disease that results in chronic anemia

28. Subject has a hematocrit that is below the normal reference range of lab used.

29. Subject is on dialysis

30. Subject has serum creatinine of >2 mg/dL.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AMCR Institute	Escondido	California	United States	92025
2	Stanford Hospital and Clinics	Palo Alto	California	United States	94305
3	SoCal Diabetes	Torrance	California	United States	90505
4	Barbara Davis Center	Aurora	Colorado	United States	80045
5	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
6	University of South Florida - USF Health	Tampa	Florida	United States	33620
7	Atlanta Diabetes Associates	Atlanta	Georgia	United States	30318
8	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho	United States	83404
9	Indiana University	Indianapolis	Indiana	United States	46202
10	University of Michigan	Ann Arbor	Michigan	United States	48109
11	Sheba Medical Center	Tel Aviv		Israel

Sponsors and Collaborators

• Medtronic Diabetes

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 29, 2019
• Statistical Analysis Plan - Oct 18, 2017

More Information

Publications

None provided.

• Responsible Party: Medtronic Diabetes
• ClinicalTrials.gov Identifier: NCT02660827
• Other Study ID Numbers: CEP 302
• First Posted: Jan 21, 2016
• Last Update Posted: Jan 26, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin

Study Results

Participant Flow

Recruitment Details	151 subjects aged 2-13 years entered study period, 1 subject withdrawn during study period, 5 subjects didn't participate continued access period after finishing study period; 145 subjects aged 2-13 years entered continued access period, 25 subjects withdrawn and 120 subjects completed continued access period.
Pre-assignment Detail	2-13 years subjects wearing MMT-670G insulin pump

Arm/Group Title	Subjects Wearing MMT-670G Insulin Pump
Arm/Group Description	Subjects wearing MMT- 670G insulin pump during Study and Continued Access period
Period Title: From Study to End of Continued Access
STARTED	151
COMPLETED	120
NOT COMPLETED	31
Period Title: From Study to End of Continued Access
STARTED	151
COMPLETED	150
NOT COMPLETED	1
Period Title: From Study to End of Continued Access
STARTED	145
COMPLETED	120
NOT COMPLETED	25

Baseline Characteristics

Arm/Group Title	Age 2-13 Yrs
Arm/Group Description	Age 2-13 Yrs Subjects wearing MMT- 670G insulin pump
Overall Participants	151
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.9 (3.3)
Sex: Female, Male (Count of Participants)
Female	69 45.7%
Male	82 54.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%
Asian	2 1.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 3.3%
White	132 87.4%
More than one race	0 0%
Unknown or Not Reported	11 7.3%
Region of Enrollment (participants) [Number]
United States	140 92.7%
Israel	11 7.3%
BMI (kg/m2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	18.4 (3.8)

Outcome Measures

1. Primary Outcome

Title	Age 2-13 Years Old Subjects Change in A1C
Description	Descriptive analysis of change in A1C from baseline to end of 3-month study period
Time Frame	Baseline and end of 3-month study period

Outcome Measure Data

Analysis Population Description

2-13 years old subjects wearing MMT-670G insulin pump; two subjects end of study A1C not collected.

Arm/Group Title	Age 2-13 Years Old Wearing MMT-670G Insulin Pump
Arm/Group Description	2-13 years old subjects wearing MMT-670G insulin pump.
Measure Participants	149
Mean (Standard Deviation) [percentage of hemoglobin]	-0.37 (0.62)

2. Secondary Outcome

Title	Age 2-13 Years Old Subjects Mean Change in % of Time in Euglycemia (70-180 mg/dL)
Description	mean change in % of time in Euglycemia (70-180 mg/dL) from baseline to 3 months study period
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

2-13 years old subjects wearing MMT-670G insulin pump.

Arm/Group Title	Age 2-13 Years Old Wearing the MMT-670G Insulin Pump
Arm/Group Description	2-13 years old subjects wearing MMT-670G insulin pump.
Measure Participants	151
Mean (Standard Deviation) [Percentage of time]	8.58 (8.84)

3. Secondary Outcome

Title	Age 2-13 Years Old Subjects Mean Change in % of Time in Hyperglycemia (> 180 mg/dL)
Description	mean change in % of time in hyperglycemia (> 180 mg/dL) from baseline to 3 months study period
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

2-13 years old subjects wearing MMT-670G insulin pump.

Arm/Group Title	Age 2-13 Years Old Wearing the MMT-670G Insulin Pump
Arm/Group Description	2-13 years old subjects wearing MMT-670G insulin pump.
Measure Participants	151
Mean (Standard Deviation) [Percent of time]	-7.39 (9.96)

4. Secondary Outcome

Title	Age 2-13 Years Old Subjects Mean Change in % of Time in Hypoglycemia (<70 mg/dL)
Description	mean change in % of time in hypoglycemia (< 70 mg/dL) from baseline to 3 months study period
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

2-13 years old subjects wearing MMT-670G insulin pump.

Arm/Group Title	Age 2-13 Years Old Wearing the MMT-670G Insulin Pump
Arm/Group Description	2-13 years old subjects wearing MMT-670G insulin pump.
Measure Participants	151
Mean (Standard Deviation) [percent of time]	-1.19 (2.58)

5. Secondary Outcome

Title	Age 2-13 Years Old - Number of Severe Hypoglycemic Event
Description	Number of severe hypoglycemic events occurred during 3-month study period.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

2-13 years old subjects wearing MMT-670G insulin pump.

Arm/Group Title	Age 2-13 Years Old Wearing the MMT-670G Insulin Pump
Arm/Group Description	2-13 years old subjects wearing MMT-670G insulin pump.
Measure Participants	151
Number [events]	0

6. Secondary Outcome

Title	Age 2-13 Years Old - Number of Diabetic Ketoacidosis (DKA) Event
Description	Number of Diabetic Ketoacidosis (DKA) events occurred during 3-month study period.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

2-13 years old subjects wearing MMT-670G insulin pump.

Arm/Group Title	Age 2-13 Years Old Wearing the MMT-670G Insulin Pump
Arm/Group Description	2-13 years old subjects wearing MMT-670G insulin pump.
Measure Participants	151
Number [events]	0

7. Secondary Outcome

Title	Age 7-13 Years Old Subjects PLGM Performance - Event Rate Without Hypoglycemia at YSI-FST <=65 mg/dL
Description	Event rate without Hypoglycemia at YSI-FST <=65 mg/dL among 105 subjects who underwent the PLGM experiments. The event rate without hypoglycemia is the number of experiments without hypoglycemia/total number of experiments and hypoglycemic events are defined based on the occurrence of 2 or more continuous YSI-FST <= 65mg/dL during in-clinic procedures.
Time Frame	Up to 12 hours after the start of PLGM period

Outcome Measure Data

Analysis Population Description

7-13 years old subjects wearing MMT-670G insulin pump, participating in clinical evaluation of the suspend before low feature.

Arm/Group Title	Age 7-13 Years Old Wearing the MMT-670G Insulin Pump
Arm/Group Description	7-13 years old subjects wearing MMT-670G insulin pump, participating in clinical evaluation of the suspend before low feature.
Measure Participants	105
Number [percentage of total experiments]	84.8

Adverse Events

Time Frame	3 months for Study period, up to 3 years for Continued Access period.
Arm/Group Title	Age 2-13 Yrs Study Period		Age 2-13 Yrs Continued Access Period
Arm/Group Description	2-13 years old subjects wearing MMT-670G insulin pump during Study period.		2-13 years old subjects wearing MMT-670G insulin pump during Continued Access period.
All Cause Mortality
	Age 2-13 Yrs Study Period		Age 2-13 Yrs Continued Access Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/151 (0%)		0/145 (0%)
Serious Adverse Events
	Age 2-13 Yrs Study Period		Age 2-13 Yrs Continued Access Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/151 (0%)		4/145 (2.8%)
Infections and infestations
Gastroenteritis	0/151 (0%)	0	1/145 (0.7%)	1
Metabolism and nutrition disorders
Hyperglycaemia	0/151 (0%)	0	1/145 (0.7%)	1
Diabetic ketoacidosis	0/151 (0%)	0	1/145 (0.7%)	1
Nervous system disorders
Hypoglycaemic seizure	0/151 (0%)	0	1/145 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Age 2-13 Yrs Study Period		Age 2-13 Yrs Continued Access Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/151 (58.3%)		113/145 (77.9%)
Blood and lymphatic system disorders
Lymphadenopathy	1/151 (0.7%)	1	0/145 (0%)	0
Ear and labyrinth disorders
Cerumen impaction	0/151 (0%)	0	1/145 (0.7%)	1
Ear pain	0/151 (0%)	0	1/145 (0.7%)	1
Gastrointestinal disorders
Abdominal pain	0/151 (0%)	0	3/145 (2.1%)	3
Abdominal pain upper	2/151 (1.3%)	2	2/145 (1.4%)	2
Coeliac disease	0/151 (0%)	0	4/145 (2.8%)	4
Constipation	1/151 (0.7%)	1	1/145 (0.7%)	1
Diarrhoea	1/151 (0.7%)	1	1/145 (0.7%)	1
Gastrointestinal disorder	0/151 (0%)	0	1/145 (0.7%)	1
Mouth ulceration	1/151 (0.7%)	1	0/145 (0%)	0
Nausea	0/151 (0%)	0	1/145 (0.7%)	1
Vomiting	2/151 (1.3%)	2	5/145 (3.4%)	5
General disorders
Ill-defined disorder	0/151 (0%)	0	1/145 (0.7%)	1
Influenza like illness	0/151 (0%)	0	2/145 (1.4%)	2
Infusion site haemorrhage	0/151 (0%)	0	1/145 (0.7%)	1
Injury associated with device	0/151 (0%)	0	1/145 (0.7%)	1
Medical device site rash	0/151 (0%)	0	1/145 (0.7%)	1
Medical device site reaction	1/151 (0.7%)	1	0/145 (0%)	0
Pain	1/151 (0.7%)	1	0/145 (0%)	0
Pyrexia	2/151 (1.3%)	2	7/145 (4.8%)	7
Immune system disorders
Food allergy	0/151 (0%)	0	1/145 (0.7%)	1
Seasonal allergy	0/151 (0%)	0	1/145 (0.7%)	1
Infections and infestations
Abscess limb	1/151 (0.7%)	1	0/145 (0%)	0
Breast cellulitis	0/151 (0%)	0	1/145 (0.7%)	1
Bronchitis	1/151 (0.7%)	1	2/145 (1.4%)	2
Cellulitis	2/151 (1.3%)	2	3/145 (2.1%)	3
Conjunctivitis	0/151 (0%)	0	6/145 (4.1%)	6
Croup infectious	0/151 (0%)	0	1/145 (0.7%)	1
Dacryocanaliculitis	1/151 (0.7%)	1	0/145 (0%)	0
Ear infection	1/151 (0.7%)	1	6/145 (4.1%)	8
Erythema infectiosum	0/151 (0%)	0	1/145 (0.7%)	1
Folliculitis	0/151 (0%)	0	1/145 (0.7%)	1
Gastroenteritis	7/151 (4.6%)	8	15/145 (10.3%)	17
Gastroenteritis viral	1/151 (0.7%)	1	6/145 (4.1%)	10
Gastrointestinal infection	1/151 (0.7%)	1	0/145 (0%)	0
Gastrointestinal viral infection	0/151 (0%)	0	2/145 (1.4%)	2
Hand-foot-and-mouth disease	0/151 (0%)	0	3/145 (2.1%)	3
Herpangina	0/151 (0%)	0	1/145 (0.7%)	1
Herpes zoster	1/151 (0.7%)	1	0/145 (0%)	0
Impetigo	1/151 (0.7%)	1	1/145 (0.7%)	1
Infectious mononucleosis	0/151 (0%)	0	1/145 (0.7%)	1
Influenza	2/151 (1.3%)	2	7/145 (4.8%)	8
Infusion site infection	1/151 (0.7%)	1	5/145 (3.4%)	5
Medical device site abscess	0/151 (0%)	0	1/145 (0.7%)	1
Medical device site infection	2/151 (1.3%)	2	0/145 (0%)	0
Molluscum contagiosum	1/151 (0.7%)	1	0/145 (0%)	0
Nasopharyngitis	5/151 (3.3%)	5	8/145 (5.5%)	12
Oral candidiasis	0/151 (0%)	0	1/145 (0.7%)	1
Otitis externa	1/151 (0.7%)	1	1/145 (0.7%)	1
Otitis media	0/151 (0%)	0	5/145 (3.4%)	5
Otitis media acute	0/151 (0%)	0	5/145 (3.4%)	6
Periumbilical abscess	0/151 (0%)	0	1/145 (0.7%)	1
Pharyngitis	0/151 (0%)	0	2/145 (1.4%)	2
Pharyngitis streptococcal	2/151 (1.3%)	2	14/145 (9.7%)	15
Pneumonia	0/151 (0%)	0	1/145 (0.7%)	1
Rhinovirus infection	1/151 (0.7%)	1	0/145 (0%)	0
Scarlet fever	0/151 (0%)	0	1/145 (0.7%)	1
Sinusitis	1/151 (0.7%)	1	6/145 (4.1%)	7
Skin infection	0/151 (0%)	0	2/145 (1.4%)	3
Staphylococcal abscess	0/151 (0%)	0	1/145 (0.7%)	1
Subcutaneous abscess	0/151 (0%)	0	2/145 (1.4%)	2
Tonsillitis	1/151 (0.7%)	1	0/145 (0%)	0
Tonsillitis streptococcal	0/151 (0%)	0	1/145 (0.7%)	1
Tooth abscess	0/151 (0%)	0	1/145 (0.7%)	1
Tooth infection	0/151 (0%)	0	1/145 (0.7%)	1
Upper respiratory tract infection	8/151 (5.3%)	8	20/145 (13.8%)	28
Urinary tract infection	1/151 (0.7%)	1	1/145 (0.7%)	1
Viral infection	5/151 (3.3%)	5	8/145 (5.5%)	9
Viral pharyngitis	1/151 (0.7%)	1	2/145 (1.4%)	2
Viral upper respiratory tract infection	1/151 (0.7%)	1	6/145 (4.1%)	6
Injury, poisoning and procedural complications
Arthropod bite	1/151 (0.7%)	1	1/145 (0.7%)	1
Avulsion fracture	0/151 (0%)	0	1/145 (0.7%)	1
Concussion	0/151 (0%)	0	3/145 (2.1%)	4
Contusion	1/151 (0.7%)	2	0/145 (0%)	0
Foot fracture	0/151 (0%)	0	1/145 (0.7%)	1
Foreign body	0/151 (0%)	0	1/145 (0.7%)	1
Greenstick fracture	0/151 (0%)	0	1/145 (0.7%)	1
Hand fracture	1/151 (0.7%)	1	3/145 (2.1%)	3
Humerus fracture	0/151 (0%)	0	2/145 (1.4%)	2
Joint injury	0/151 (0%)	0	1/145 (0.7%)	1
Ligament sprain	2/151 (1.3%)	2	4/145 (2.8%)	4
Limb injury	1/151 (0.7%)	1	1/145 (0.7%)	1
Meniscus injury	0/151 (0%)	0	1/145 (0.7%)	1
Radius fracture	0/151 (0%)	0	1/145 (0.7%)	1
Scar	0/151 (0%)	0	2/145 (1.4%)	2
Skin abrasion	1/151 (0.7%)	1	0/145 (0%)	0
Skin laceration	0/151 (0%)	0	2/145 (1.4%)	2
Torus fracture	1/151 (0.7%)	1	2/145 (1.4%)	2
Upper limb fracture	0/151 (0%)	0	1/145 (0.7%)	1
Wrist fracture	0/151 (0%)	0	2/145 (1.4%)	2
Investigations
Blood ketone body increased	1/151 (0.7%)	1	0/145 (0%)	0
Helicobacter test positive	0/151 (0%)	0	1/145 (0.7%)	1
Metabolism and nutrition disorders
Acetonaemia	0/151 (0%)	0	1/145 (0.7%)	1
Dehydration	1/151 (0.7%)	1	0/145 (0%)	0
Diabetic ketoacidosis	0/151 (0%)	0	1/145 (0.7%)	1
Hyperglycaemia	56/151 (37.1%)	146	70/145 (48.3%)	372
Hypoglycaemia	1/151 (0.7%)	1	5/145 (3.4%)	5
Ketosis	1/151 (0.7%)	1	1/145 (0.7%)	1
Musculoskeletal and connective tissue disorders
Muscle spasms	1/151 (0.7%)	1	0/145 (0%)	0
Musculoskeletal pain	1/151 (0.7%)	1	0/145 (0%)	0
Osteochondrosis	0/151 (0%)	0	1/145 (0.7%)	1
Pain in extremity	1/151 (0.7%)	1	5/145 (3.4%)	5
Scoliosis	0/151 (0%)	0	2/145 (1.4%)	2
Temporomandibular joint syndrome	0/151 (0%)	0	1/145 (0.7%)	1
Nervous system disorders
Headache	4/151 (2.6%)	4	2/145 (1.4%)	2
Migraine	1/151 (0.7%)	1	0/145 (0%)	0
Presyncope	0/151 (0%)	0	1/145 (0.7%)	1
Syncope	1/151 (0.7%)	1	0/145 (0%)	0
Psychiatric disorders
Attention deficit hyperactivity disorder	0/151 (0%)	0	1/145 (0.7%)	1
Depression	0/151 (0%)	0	1/145 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/151 (0.7%)	1	0/145 (0%)	0
Cough	1/151 (0.7%)	1	6/145 (4.1%)	7
Dyspnoea	0/151 (0%)	0	1/145 (0.7%)	1
Laryngeal oedema	0/151 (0%)	0	1/145 (0.7%)	1
Nasal congestion	3/151 (2%)	3	1/145 (0.7%)	1
Nasal polyps	0/151 (0%)	0	1/145 (0.7%)	1
Oropharyngeal pain	1/151 (0.7%)	1	4/145 (2.8%)	4
Rhinitis allergic	0/151 (0%)	0	2/145 (1.4%)	2
Sleep apnoea syndrome	1/151 (0.7%)	1	1/145 (0.7%)	1
Upper respiratory tract congestion	0/151 (0%)	0	1/145 (0.7%)	1
Skin and subcutaneous tissue disorders
Acne	0/151 (0%)	0	1/145 (0.7%)	1
Alopecia	1/151 (0.7%)	1	0/145 (0%)	0
Dermatitis	2/151 (1.3%)	2	2/145 (1.4%)	2
Dermatitis allergic	0/151 (0%)	0	1/145 (0.7%)	1
Dermatitis contact	0/151 (0%)	0	1/145 (0.7%)	1
Eczema	2/151 (1.3%)	3	0/145 (0%)	0
Erythema	0/151 (0%)	0	1/145 (0.7%)	1
Lipoatrophy	1/151 (0.7%)	1	0/145 (0%)	0
Pityriasis rosea	0/151 (0%)	0	1/145 (0.7%)	1
Rash	1/151 (0.7%)	1	5/145 (3.4%)	5
Rash maculo-papular	1/151 (0.7%)	1	0/145 (0%)	0
Skin irritation	5/151 (3.3%)	5	1/145 (0.7%)	1
Urticaria	0/151 (0%)	0	1/145 (0.7%)	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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.