Study to Evaluate Safety and Efficacy of Dapagliflozin and Saxagliptin in Patients With Type 2 Diabetes Mellitus (T2DM) Aged 10 to Below 18 Years Old

NCT ID: NCT03199053

Last Updated: 2024-06-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

256 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-11

Study Completion Date

2024-01-03

Brief Summary

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The primary objective of this study is to determine if there will be a greater mean reduction from baseline in glycated hemoglobin (HbA1c) achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin or saxagliptin compared to placebo in paediatric T2DM patients with HbA1c levels of 6.5 to 10.5% on diet and exercise and metformin, insulin, or metformin plus insulin.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Eligible subjects with HbA1c of 6.5% to 10.5% at screening will be randomized 1:1:1 to receive dapagliflozin 5 mg, saxagliptin 2.5 mg, or placebo. Blinded HbA1c assessment will be performed at Week 12. All subjects with Week 12 HbA1c \< 7% will remain on previously assigned randomized treatment. Subjects taking dapagliflozin with Week 12 HbA1c ≥ 7% will be re-randomized in a 1:1 ratio to continue on the low-dose treatment (dapagliflozin 5 mg) or up titrate to the high-dose treatment (dapagliflozin 10 mg). Subjects taking saxagliptin with Week 12 HbA1c ≥ 7% will be re-randomized in a 1:1 ratio to continue on the low-dose treatment (saxagliptin 2.5 mg) or up-titrate to the high-dose treatment (saxagliptin 5 mg). Subjects taking placebo with Week 12 HbA1c ≥ 7% will continue on placebo treatment. All placebo subjects and all subjects taking saxagliptin or dapagliflozin with HbA1c \< 7% at Week 12 will go through a dummy 2nd randomization process for maintaining the blinding.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
sponsor

Study Groups

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Low dose Dapagliflozin

Oral route. Start with a low dose of dapagliflozin administered once daily and remain on the low dose regardless of your HbA1c at week 12.

Group Type EXPERIMENTAL

Dapagliflozin

Intervention Type DRUG

Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily

Low dose/high dose Dapagliflozin

Oral route. Start with a low dose of Dapagliflozin administered once daily and up titrate to the high dose Dapagliflozin administered once daily if HbA1c \>= 7% at week 12

Group Type EXPERIMENTAL

Dapagliflozin

Intervention Type DRUG

Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily

Low dose Saxagliptin

Oral route. Start with a low dose of saxagliptin administered once daily and remain on the low dose regardless of your HbA1c at week 12

Group Type EXPERIMENTAL

Saxagliptin

Intervention Type DRUG

Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily

Low dose/high dose Saxagliptin

Oral route. Start with a low dose of saxagliptin administered once daily and up titrate to the high dose if HbA1c \>= 7% at week 12

Group Type EXPERIMENTAL

Saxagliptin

Intervention Type DRUG

Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily

Placebo arm

Oral route. Placebo tablets administered for 52 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo to dapagliflozin 5mg and 10 mg/saxagliptin 2.5 mg and 5 mg, Tablets, oral, Once daily

Interventions

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Dapagliflozin

Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily

Intervention Type DRUG

Saxagliptin

Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily

Intervention Type DRUG

Placebo

Matching placebo to dapagliflozin 5mg and 10 mg/saxagliptin 2.5 mg and 5 mg, Tablets, oral, Once daily

Intervention Type DRUG

Other Intervention Names

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Forxiga Onglyza

Eligibility Criteria

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Inclusion Criteria

* Signed Written Informed Consent
* Target Population
* Previously diagnosed with Type 2 Diabetes Mellitus by World Health Organization/ADA criteria
* HbA1c between 6.5% and 10.5% obtained at screening.
* Currently on diet and exercise and stable dose of at least 1000 mg metformin (IR or XR) for a minimum of 8 weeks, or stable dose of insulin for a minimum of 8 weeks, or a stable combination of at least 1000 mg metformin (IR or XR) and insulin for a minimum of 8 weeks prior to randomization. For those children on insulin, investigators will confirm that attempts at removing insulin from the subject's therapeutic regimen had been previously made but had not been successful.
* Age and Reproductive Status
* Male and female patients eligible if 10 years of age, up to but not including 18 years of age at the time of enrollment/screening. At least 30% of total subjects will be between the ages of 10 and 14 years and at least one third, but no more than two thirds, female subjects.
* Women of childbearing potential must have a negative pregnancy test within 24 hours prior to the start of study drug.
* Women must not be breastfeeding.
* Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs: saxagliptin, and dapagliflozin, plus 5 half-lives of study drugs or 30 days (whichever is longer), plus 30 days (duration of ovulatory cycle) for a total of 60 days post treatment completion.

Exclusion Criteria

* Target Disease Exceptions
* Presence of Type 1 diabetes, as demonstrated by Preexisting diagnosis of Type 1 diabetes,
* Previous diagnosis of monogenic etiology of Type 2 diabetes
* Diabetes ketoacidosis (DKA) within 6 months of screening
* Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study:
* Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics, other antidiabetes medications not otherwise specified.
* Sixteen weeks: thiazolidinediones, DPP-4 inhibitors (with no reported medication related AEs related to DPP-4 inhibitors), sodium glucose cotransporter-2 (SGLT-2) inhibitors (with no reported medication related AEs related to SGLT-2 inhibitors)
* Initiation or discontinuation of prescription or non-prescription weight loss drugs within 8 weeks of screening. Use of prescription or non-prescription weight loss drugs must be stable during the study.
* Medical History and Concurrent Diseases
* Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding
* History of unstable or rapidly progressive renal disease
* History of unresolved vesico-ureteral reflux
* History of or current, acute or chronic pancreatitis
* History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis
* Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma)
* Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for \> 4 weeks within 3 months prior to the Day 1 visit
* Physical and Laboratory Test Findings
* Abnormal renal function,
* An abnormal thyroid-stimulating hormone (TSH) value at enrollment will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded.
* Hematuria (confirmed by microscopy at screening) with no explanation as judged by the Investigator up to randomization.
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2× upper limit of normal (ULN), or clinically significant hepatic disease.
* Serum total bilirubin (TB) \> 2x ULN unless exclusively caused by Gilbert's syndrome
* Positive serologic evidence of current infectious liver disease including anti hepatitis A virus (HAV) (IgM), hepatitis B surface antigen (HBsAg), or anti hepatitis C virus (HCV). Patients who have isolated positive anti-hepatitis B surface antibodies may be included.
* Anemia of any etiology
* Volume-depleted subjects.
* Allergies and Adverse Drug Reaction
* Known allergy, sensitivity or contraindication to any study drug or its excipient/vehicle
* Subject is currently abusing alcohol or other drugs or has done so within the last 6 months prior to the screening visit.
* Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and Sponsor/designee approval is required.)
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
* Psychiatric or cognitive disorder that will, in the opinion of investigators, limit the subject's ability to comply with the study medications and monitoring.
* Subjects who have contraindications to therapy as outlined in the saxagliptin and dapagliflozin Investigator Brochure or local package inserts.
* Participation and receiving IP in another clinical study during the prior 3 months
Minimum Eligible Age

10 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Sacramento, California, United States

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New Haven, Connecticut, United States

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Hialeah, Florida, United States

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Hialeah, Florida, United States

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Hollywood, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami Springs, Florida, United States

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Atlanta, Georgia, United States

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Atlanta, Georgia, United States

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Idaho Falls, Idaho, United States

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Neptune City, New Jersey, United States

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Memphis, Tennessee, United States

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Memphis, Tennessee, United States

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Edinburg, Texas, United States

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Harlingen, Texas, United States

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McAllen, Texas, United States

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San Antonio, Texas, United States

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Charlottesville, Virginia, United States

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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CABA, , Argentina

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Ciudad de Buenos Aires, , Argentina

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San Miguel de Tucumán, , Argentina

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San Miguel de Tucumán, , Argentina

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Blacktown, , Australia

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Brasília, , Brazil

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Curitiba, , Brazil

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Fortaleza, , Brazil

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Fortaleza, , Brazil

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Passo Fundo, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Ribeirão Preto, , Brazil

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Santa Maria, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Montreal, Quebec, Canada

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Santiago, , Chile

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Armenia, , Colombia

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Barranquilla, , Colombia

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Tampere, , Finland

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Ahmedabad, , India

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Aurangabad, , India

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Bangalore, , India

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Bikaner, , India

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Chandigarh, , India

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Coimbatore, , India

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Hyderabad, , India

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Kolkata, , India

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Kozhikode, , India

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Nashik, , India

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Pune, , India

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Visakhapatnam, , India

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Haifa, , Israel

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Ancona, , Italy

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Napoli, , Italy

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Roma, , Italy

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George Town, , Malaysia

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Ipoh, , Malaysia

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Johor Bahru, , Malaysia

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Klang, , Malaysia

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Kota Kinabalu, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuching, , Malaysia

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Malacca, , Malaysia

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Putrajaya, , Malaysia

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Seremban, , Malaysia

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Seri Manjung, , Malaysia

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Taiping, , Malaysia

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Boca del Rio, , Mexico

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Celaya, , Mexico

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Ciudad Madero, , Mexico

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Cuernavaca, , Mexico

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Cuernavaca, , Mexico

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Culiacán, , Mexico

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Durango, , Mexico

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Guadalajara, , Mexico

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Juriquilla, , Mexico

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Mérida, , Mexico

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México, , Mexico

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México, D.F., , Mexico

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Monterrey, , Mexico

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Monterrey, , Mexico

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San Juan del Río, , Mexico

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Veracruz, , Mexico

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Zapopan, , Mexico

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Grafton, , New Zealand

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Tauranga, , New Zealand

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Wellington, , New Zealand

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Quezon City, , Philippines

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Quezon City, , Philippines

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San Fernando City, , Philippines

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Warsaw, , Poland

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Izhevsk, , Russia

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Moscow, , Russia

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Ufa, , Russia

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Daejeon, , South Korea

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Incheon, , South Korea

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Wŏnju, , South Korea

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Hat Yai, , Thailand

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Aydin, , Turkey (Türkiye)

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Bursa, , Turkey (Türkiye)

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Eskişehir, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kocaeli, , Turkey (Türkiye)

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Kurupelit, , Turkey (Türkiye)

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Manisa, , Turkey (Türkiye)

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Dnipro, , Ukraine

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Kyiv, , Ukraine

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Vinnytsia, , Ukraine

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Birmingham, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Middlesbrough, , United Kingdom

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Nottingham, , United Kingdom

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Countries

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United States Argentina Australia Brazil Canada Chile Colombia Finland India Israel Italy Malaysia Mexico New Zealand Philippines Poland Russia South Korea Taiwan Thailand Turkey (Türkiye) Ukraine United Kingdom

References

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Shehadeh N, Barrett T, Galassetti P, Karlsson C, Monyak J, Iqbal N, Tamborlane WV. Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes. NEJM Evid. 2023 Dec;2(12):EVIDoa2300210. doi: 10.1056/EVIDoa2300210. Epub 2023 Oct 4.

Reference Type DERIVED
PMID: 38320500 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-005042-66

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D1680C00019

Identifier Type: -

Identifier Source: org_study_id

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