1. A clinical study to test how the drug (Exenatide) works on children with Type 2 Diabetes

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2018/02/011717
• Date of registration: 05-02-2018
• Prospective Registration: Yes
• Primary sponsor: Amylin LLC a wholly owned subsidiary of AstraZeneca
• Public title: 1. A clinical study to test how the drug (Exenatide) works on children with Type 2 Diabetes
• Scientific title: Safety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents with Type 2 Diabetes
• Date of first enrolment: 25-02-2018
• Target sample size: 195
• Recruitment status: Not Yet Recruiting
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=22722
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
• Phase: Phase 3

Countries of recruitment

Brazil, China, India, Mexico, Philippines, Republic of Korea, Russian Federation, South Africa, United States of America

Contacts

• Name: Dr Hardik Vasnawala
• Affiliation: Astra Zeneca India

• Name: Alexandria Cairns
• Affiliation: Astra Zeneca India

Key inclusion & exclusion criteria

Inclusion criteria: Patients are eligible to be included in the study only if they meet all of the following criteria:

[1] are a male or a female between ages 10 to 17 years, inclusive. The number of patients >=17 years of age will be limited to no more than 10% of patients in each treatment arm

[2] have a history of type 2 diabetes with the original diagnosis based on at least one American Diabetes Association (ADA) diagnostic criteria

[3] have been treated with metformin, an SU, or both metformin and an SU (with or without diet and exercise), for at least 3 months or are naïve to anti-diabetes agents and being treated with diet and exercise alone. The dose of oral agent(s) should be stable for the 30 days prior to the screening visit

[4] have fasting C-peptide >0.6 ng/mL

[5] have no antibodies to glutamic acid decarboxylase (GAD65) or islet cell antigen (ICA512)

[6] have HbA1c between 6.5% and 10.5%, inclusive

[7] present an appropriately signed assent form

[8] a parent or adult guardian agrees in writing to participate in the patientâ??s treatment by signing a consent form

[9] both the patient and parent or responsible adult guardian are able to understand and comply with a lifestyle modification program

[10] the investigator determines that patient and parent or responsible adult guardian are able to fully participate in and likely to complete the trial.



Disease Diagnostic Criteria

For the purposes of this study, patients with type 2 diabetes are defined by:

-diagnosis of type 2 diabetes, as determined by ADA diagnostic criteria and

antibody testing, documented and confirmed in the patientâ??s medical record,

which includes laboratory determinations consistent with one or more of the

following in the patientâ??s medical history:

I)fasting blood glucose ï?³126 mg/dL (7.0 mmol/L)

ii) random blood glucose ï?³200 mg/dL (11.1 mmol/L)

iii) two-hour OGTT (Oral Glucose Tolerance Test) ï?³200 mg/dL (11.1

mmol/L)

AND one or more of the following:

I) no antibodies to GAD65

OR

ii) no antibodies to islet cell antigen (ICA512)


Exclusion criteria: Patients will be excluded from the study if they meet any of the following criteria:

[11] are the children or immediate family members of either Amylin, Bristol- Myers Squibb, or AstraZeneca employees or investigator site personnel directly affiliated with this study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted

[12] have received treatment within the last 60 days with a drug that has not received regulatory approval for any indication at the time of study entry

[13] have previously been exposed to exenatide or, completed or withdrawn from this study or any other study investigating exenatide

[14] are unwilling or unable to inject the study medication

[15] have a genetic syndrome or disorder other than diabetes known to affect glucose tolerance

[16] have a known allergy or hypersensitivity to exenatide or excipients contained in the agent

[17] have used an alpha-glucosidase inhibitor, a meglitinide, or pramlintide for

more than 1 week during the 3 months prior to screening

[18] currently use inhaled steroids at a dose equal to or above 1000 ï?­g Floventï?? (fluticasone propionate) daily

[19] have used oral steroids within the last 60 days or more than 20 days use within the past year

[20] have used a TZD within 120 days prior to screening

[21] have used any weight loss medication(s) within 30 days of screening

[22] are sexually active female of childbearing potential who is unwilling to appropriately use TWO methods of birth control (for example, use of oral contraceptives; condoms with contraceptive foam; or abstinence) for the duration of the study

[23] are female who is pregnant or planning to become pregnant within 6 months of study screening

[24] are female who is lactating.

[25] have history of renal disease, or serum creatinine >1.6 mg/dL (141.4 μmol/L) (males) or >1.4 mg/dL (123.8 μmol/L) (females) [26] have hepatic dysfunction, defined by aspartate (AST) or alanine (ALT) transaminase >3.0 times the upper limit of normal (ULN)

[27] have had at least 1 episode of diabetic ketoacidosis after receiving antidiabetes medication. A history of diabetic ketoacidosis at the time of diagnosis will not be an exclusion criterion

[28] have physical limitations that prevent participation in lifestyle intervention

[29] have admitted use of anabolic steroids within the past 60 days

[30] have an active or untreated malignancy, or have been in remission from clinically significant malignancy (other than in situ carcinomas of the cervix) for less than 5 years

[31] have investigator-determined significant organ system illness or condition,

including but not limited to psychiatric or developmental disorder that prevent participation in lifestyle intervention

[32] fail to satisfy the investigator of suitability to participate for any other reason

[33] have used insulin for more than 10 weeks during the 3 months prior to screening



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Type 2 Diabetes Health Condition 2: E119- Type 2 diabetes mellitus without complications

Intervention(s)

Intervention1: Intervention Agent:

1. Exenatide 5 μg
2. Exenatide 10 μg

: Exenatide 5 μg twice daily, for 28 Weeks
Exenatide 10 μg twice daily, for 28 Weeks


Control Intervention1: Placebo: Placebo, twice daily (volume of injection equivalent to exenatide 5 μg or exenatide 10 μg)for 28 Weeks

Primary Outcome(s)

The primary objective of this study is to test the hypothesis that glycemic control, as measured

by change in hemoglobin A1c (HbA1c) from baseline to endpoint, with exenatide is superior (in at least 1 of the exenatide treatment arms), to that of placebo after 28 weeks of treatment in

adolescent patients with type 2 diabetes who are naïve to antidiabetes agents, or patients who are being treated with metformin, an Sulfonylurea, or a combination of metformin and an Sulfonylurea

Timepoint: 2. The data collected from the patients was assessed for safety when 25% and 50% of patients had been randomised. safety will be assessed one more time when 75% of patients are randomised. Final safety and efficacy assessment will be made at the end of the study, when all randomised patients have completed their 28 weeks treatment.

Secondary Outcome(s)

the proportion of patients discontinuing the study due to failure to maintain

glycemic control

Timepoint: Visit 11 or Early Discontinuation

body weightTimepoint: Visit 1, 2, 3, 5, 7, 9, 11 and Early Discontinuation

self-monitored blood glucose (SMBG) measurements before and 2 hours after the

two main meals of the day

Timepoint: Visit 3 and 11

safety and tolerability including reporting of adverse events, antibodies to

exenatide, calcitonin, carcinoembryonic antigen (CEA), vital signs,

electrocardiograms (ECGs), laboratory measurements, urinalysis, and pubertal

assessment

Timepoint: During the entire study period

fasting serum glucose (FSG)Timepoint: Visit 1, 3, 11, Unscheduled Visit and Early Discontinuation

the incidence and rate of hypoglycemiaTimepoint: Visit 3, 5, 7 11 and Early Discontinuation

beta-cell function and insulin sensitivity as measured by homeostasis model

assessments (HOMA-B, HOMA-S) (Matthews et al. 1985)Timepoint: Visit 3, 11 and Early Discontinuation

fasting serum insulin concentrationsTimepoint: Visit 3, 11 and Early Discontinuation

The secondary objectives of the study are to compare exenatide 5 μg twice daily and exenatide

10 μg twice daily versus each other and versus placebo with regards to:

I)the proportion of patients achieving an HbA1c at endpoint of 7%, â?¤6.5%, and

6.5%

Timepoint: Baseline to Endpoint

Secondary ID(s)

H8O-MC-GWBQ Amendment Version (d) Dated 16 May 2013

Source(s) of Monetary Support

Amylin, LLC (a wholly owned subsidiary of AstraZeneca) AstraZeneca AB, SE-151 85 Södertälje, Sweden

Secondary Sponsor(s)

AstraZeneca Pharma India Limited

Ethics review

Status: Approved
Approval date: 27/02/2017
Contact:

Institutional Ethics Committee of Kovai Diabetes Speciality Centre and Hospital, 15, Vivekananda Road, Ramnagar, Coimbatore-641009, Tamil Nadu, India.

Status: Approved
Approval date: 02/06/2017
Contact:

Institutional Ethics Committee

Status: Approved
Approval date: 17/08/2017
Contact:

Narayana Hrudayalaya Medical Ethics Committee

Status: Approved
Approval date: 27/09/2017
Contact:

institutional Ethics Committee

Status: Not Approved
Approval date:
Contact:

Ethics Committee, Andhra Medical College

Status: Not Approved
Approval date:
Contact:

Institute Ethics Committee, All India Institute of Medical Sciences

Status: Not Approved
Approval date:
Contact:

Institutional Ethics committee

Status: Not Approved
Approval date:
Contact:

Institutional Ethics Committee - Fortis Hospital

Status: Not Approved
Approval date:
Contact:

Medanta Institutional Ethics Committee