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A Clinical Trial Comparing Glycaemic Control and Safety of Insulin Degludec/Liraglutide (IDegLira) Versus Insulin Glargine (IGlar) as add-on Therapy to SGLT2i in Subjects With Type 2 Diabetes Mellitus (DUALTM IX)

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ClinicalTrials.gov Identifier: NCT02773368
Recruitment Status : Completed
First Posted : May 16, 2016
Results First Posted : October 23, 2018
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Tracking Information
First Submitted Date  ICMJE May 13, 2016
First Posted Date  ICMJE May 16, 2016
Results First Submitted Date  ICMJE September 24, 2018
Results First Posted Date  ICMJE October 23, 2018
Last Update Posted Date August 11, 2020
Actual Study Start Date  ICMJE May 23, 2016
Actual Primary Completion Date September 26, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
Change in HbA1c (Glycosylated Haemoglobin) [ Time Frame: Week 0, Week 26 ]
The mean change from baseline (week 0) in HbA1c values evaluated after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2016)
Change in HbA1c (glycosylated haemoglobin) [ Time Frame: Week 0, Week 26 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
  • Change in Body Weight [ Time Frame: Week 0, Week 26 ]
    The mean change from baseline (week 0) in body weight evaluated after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Number of Treatment-emergent Severe or BG (Blood Glucose) Confirmed Symptomatic Hypoglycaemic Episodes [ Time Frame: Week 0-26 ]
    Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe (subjects who were not able to self-treat) and/or BG confirmed by a plasma glucose values <3.1 mmol/L (56 mg/dL) with accompanied symptoms consistent with hypoglycaemia.
  • Insulin Dose, Total Daily Dose (U) [ Time Frame: After 26 weeks ]
    Actual daily total insulin dose (Units) was evaluated after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Change in Fasting Plasma Glucose (FPG) [ Time Frame: Week 0, Week 26 ]
    Change from baseline (week 0) in FPG was evaluated after 26 weeks of randomised treatment.
  • Number of Treatment-emergent Adverse Events [ Time Frame: Week 0-26 ]
    Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 26. TEAE was defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.
  • Responder (Yes/No) for HbA1c Below 7.0% [ Time Frame: After 26 weeks ]
    The proportion of subjects achieving pre-defined HbA1c targets <7.0% after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Responder After 26 Weeks (Yes/No) for: HbA1c < 7.0% Without Weight Gain [ Time Frame: After 26 weeks ]
    The proportion of subjects achieving pre-defined HbA1c targets <7.0% without weight gain after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Responder After 26 Weeks (Yes/No) for: HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment [ Time Frame: After 26 weeks ]
    The proportion of subjects achieving pre-defined HbA1c targets <7.0% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Responder After 26 Weeks (Yes/No) for: HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment and Without Weight Gain [ Time Frame: After 26 weeks ]
    The proportion of subjects achieving pre-defined HbA1c targets <7.0% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment and without weight gain. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% [ Time Frame: After 26 weeks ]
    The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5% after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% Without Weight Gain [ Time Frame: After 26 weeks ]
    The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5% without weight gain after 26 weeks of randomised treatment. The results are based on retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment [ Time Frame: After 26 weeks ]
    The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5%without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment and Without Weight Gain [ Time Frame: After 26 weeks ]
    The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5%without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment and without weight gain. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
  • Change From Baseline After 26 Weeks in Waist Circumference [ Time Frame: After 26 weeks ]
    Mean change from baseline in waist circumference after 26 weeks of randomised treatment.
  • Change From Baseline in Fasting Lipid Profile: Cholesterol [ Time Frame: After 26 weeks ]
    The values of total cholesterol from fasting lipid profile after 26 weeks of randomised treatment.
  • Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein Cholesterol (LDL Cholesterol) [ Time Frame: After 26 weeks ]
    The values of LDL cholesterol from fasting lipid profile after 26 weeks of randomised treatment.
  • Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein Cholesterol (HDL Cholesterol) [ Time Frame: After 26 weeks ]
    The values of HDL cholesterol from fasting lipid profile after 26 weeks of randomised treatment.
  • Change From Baseline in Fasting Lipid Profile: Very-low-density Lipoprotein Cholesterol (VLDL Cholesterol) [ Time Frame: After 26 weeks ]
    The values of VLDL cholesterol from fasting lipid profile after 26 weeks of randomised treatment.
  • Change From Baseline in Fasting Lipid Profile: Triglycerides [ Time Frame: After 26 weeks ]
    The values of triglycerides from fasting lipid profile after 26 weeks of randomised treatment.
  • Change From Baseline in Fasting Lipid Profile: Free Fatty Acids [ Time Frame: After 26 weeks ]
    The values of free fatty acids from fasting lipid profile after 26 weeks of randomised treatment.
  • Change From Baseline in the 9-point Self-measured Plasma Glucose (SMPG) Profile [ Time Frame: After 26 weeks ]
    Change in 9-point SMPG profile was evaluated after 26 weeks of randomised treatment. SMPG measurements at baseline and week 26 are presented here at the following mentioned time points:1) Before breakfast, 2) 90 mins after the start of Breakfast, 3) Before lunch, 4) 90 mins after the start of lunch, 5) Before dinner, 6) 90 mins after the start of dinner, 7) At bedtime, 8) At 4 AM, 9) Before breakfast the following day.
  • Change From Baseline in Self-measured Plasma Glucose (SMPG) 9-point Profile: Mean of the 9-point Profile [ Time Frame: After 26 weeks ]
    Change in mean of the 9-point profile SMPG was evaluated after 26 weeks of randomised treatment. 9-point profile SMPG was measured at the following mentioned time points:1) Before breakfast, 2) 90 mins after the start of Breakfast, 3) Before lunch, 4) 90 mins after the start of lunch, 5) Before dinner, 6) 90 mins after the start of dinner, 7) At bedtime, 8) At 4 AM, 9) Before breakfast the following day.
  • Change From Baseline in SMPG 9-point Profile: Prandial Plasma Glucose Increments (From Before Meal to 90 Min After Breakfast, Lunch and Dinner). The Mean Increment Over All Meals Will be Derived as the Mean of All Available Meal Increments [ Time Frame: After 26 weeks ]
    Mean prandial plasma glucose increments for each meal (from before meal to 90 min after breakfast, lunch and dinner) was evaluated after 26 weeks of randomised treatment. The mean increment over all meals was derived as the mean of all available meal increments are presented here.
  • Change From Baseline in Systolic Blood Pressure [ Time Frame: After 26 weeks ]
    Change from baseline (week 0) in systolic blood pressure (BP) was evaluated after 26 weeks of randomised treatment.
  • Change From Baseline in Diastolic Blood Pressure [ Time Frame: After 26 weeks ]
    Change from baseline (week 0) in diastolic blood pressure was evaluated after 26 weeks of randomised treatment.
  • Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 26 Weeks [ Time Frame: Week 0-26 ]
    Number of treatment-emergent nocturnal severe or BG confirmed symptomatic hypoglycaemic episodes (00:01-05:59 - inclusive) during 26 weeks of randomised treatment.
  • Number of Treatment-emergent Hypoglycaemic Episodes According to ADA Definition During 26 Weeks [ Time Frame: Week 0-26 ]
    American Diabetes Association (ADA) classification of hypoglycaemic episodes: 1)Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level. 2) Documented symptomatic: PG ≤3.9 mmol/L with symptoms. 3) Asymptomatic: PG ≤3.9 mmol/L without symptoms. 4) Probable symptomatic: No measurement with symptoms. 5) Pseudo: PG >3.9 mmol/L with symptoms. 6) Unclassifiable.
  • Change From Baseline in Clinical Evaluation After 26 Weeks: Electrocardiogram (ECG) [ Time Frame: After 26 weeks ]
    Reported results are ECG findings at screening and week 26 of randomised treatment. Since the values measured at the baseline (week 0) were not collected, the screening data (week -2, which is <= 2 weeks before baseline) is presented here. The findings are categorised as: 1) Normal. 2) Abnormal (not clinically significant [NCS]). 3) Abnormal (clinically significant [CS]). 4) Missing.
  • Change From Baseline in Clinical Evaluation After 26 Weeks: Eye Examination: Fundoscopy/Fundus Photography [ Time Frame: After 26 weeks ]
    Reported results are fundus photography/fundoscopy (for both left and right eye) findings at screening and week 26 of randomised treatment. Since the values measured at the baseline (week 0) were not collected, the screening data (week -2, which is <= 2 weeks before baseline) is presented here. The findings are categorised as: 1) Normal. 2) Abnormal (not clinically significant [NCS]). 3) Abnormal (clinically significant [CS]). 4) Missing.
  • Change From Baseline in Clinical Evaluation After 26 Weeks: Pulse Rate [ Time Frame: After 26 weeks ]
    Change from baseline (week 0) in pulse rate was evaluated after 26 weeks of randomised treatment.
  • Change From Baseline in Patient Reported Outcomes (PROs) After 26 Weeks: Summary Scores of Medical Outcomes Study 36-item Short Form (SF-36v2) [ Time Frame: After 26 weeks ]
    The Short Form (SF)-36v2™ patient reported outcomes (PRO) questionnaire was used to assess the subject's overall health related quality of life (HRQoL). PRO questionnaire (SF-36v2™) measured the HRQoL which contains 36 items covering 8 domains of physical and mental health status. The raw scale scores from the SF-36 were transformed to a 0-100 scale scores (where higher scores indicated a better health status) which is further converted to norm-based scores using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 2009 reference population . The total/overall (SF-36v2™) scores for physical and mental health from baseline to week 26 are presented here.
  • Change From Baseline in Patient Reported Outcomes (PROs) After 26 Weeks: Summary Scores of Treatment Related Impact Measure for Diabetes (TRIM-D) [ Time Frame: After 26 weeks ]
    The patient reported outcomes are calculated based on TRIM-D questionnaire. The TRIM-D questionnaire consists of 5 sub-domains (treatment burden, daily life, diabetes management, compliance and psychological health), where each question is scored to a 1-5-point scale with a higher score indicating a better health state (less negative impact). Mean TRIM-D domain scores and the total scores are later transformed to a 0-100 scale for analysis. Summary scores from baseline and week 26 for total/overall scores are presented here.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2016)
  • Change in body weight [ Time Frame: Week 0, Week 26 ]
  • Number of treatment-emergent severe confirmed symptomatic hypoglycaemic episodes [ Time Frame: Week 0-26 ]
  • Number of BG (blood glucose) confirmed symptomatic hypoglycaemic episodes [ Time Frame: Week 0-26 ]
  • Insulin dose, total daily dose (U) [ Time Frame: After 26 weeks ]
  • Responder (Yes/No) for HbA1c below 7.0% [ Time Frame: After 26 weeks ]
  • Change in fasting plasma glucose (FPG) [ Time Frame: Week 0, Week 26 ]
  • Number of treatment-emergent adverse events [ Time Frame: Week 0-26 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Trial Comparing Glycaemic Control and Safety of Insulin Degludec/Liraglutide (IDegLira) Versus Insulin Glargine (IGlar) as add-on Therapy to SGLT2i in Subjects With Type 2 Diabetes Mellitus
Official Title  ICMJE A Clinical Trial Comparing Glycaemic Control and Safety of Insulin Degludec/Liraglutide (IDegLira) Versus Insulin Glargine (IGlar) as add-on Therapy to SGLT2i in Subjects With Type 2 Diabetes Mellitus. DUALTM IX - Add-on to SGLT2i
Brief Summary This trial is conducted globally. The aim of this trial is comparing glycaemic control and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine (IGlar) as add-on therapy to SGLT2i (sodium-glucose cotransporter 2 inhibitors) in subjects with type 2 diabetes mellitus.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diabetes
  • Diabetes Mellitus, Type 2
Intervention  ICMJE
  • Drug: insulin degludec/liraglutide
    IDegLira will be given subcutaneously ( s.c., under the skin) once daily.
  • Drug: insulin glargine
    IGlar will be given subcutaneously ( s.c., under the skin) once daily.
Study Arms  ICMJE
  • Experimental: IDegLira
    Intervention: Drug: insulin degludec/liraglutide
  • Active Comparator: IGlar
    Intervention: Drug: insulin glargine
Publications * Philis-Tsimikas A, Billings LK, Busch R, Portillo CM, Sahay R, Halladin N, Eggert S, Begtrup K, Harris S. Superior efficacy of insulin degludec/liraglutide versus insulin glargine U100 as add-on to sodium-glucose co-transporter-2 inhibitor therapy: A randomized clinical trial in people with uncontrolled type 2 diabetes. Diabetes Obes Metab. 2019 Jun;21(6):1399-1408. doi: 10.1111/dom.13666. Epub 2019 Apr 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 26, 2017)
420
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2016)
416
Actual Study Completion Date  ICMJE October 23, 2017
Actual Primary Completion Date September 26, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE Inclusion Criteria: - Male or female, age at least 18 years at the time of signing informed consent - Subjects diagnosed (clinically) with type 2 diabetes mellitus - HbA1c 7.0-11.0% [53-97 mmol/mol] (both inclusive) by central laboratory analysis - Body mass index (BMI) equal to or above 20 kg/m^2 and below 40 kg/m^2 - Insulin naïve subjects; however short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as well as prior insulin treatment for gestational diabetes - A stable daily dose for at least 90 days prior to the day of screening of any SGLT2i in monotherapy or in combination with metformin ± DPP4i ± pioglitazone. Use of pioglitazone is not allowed in subjects treated with dapagliflozin Exclusion Criteria: - Receipt of any investigational medicinal product within 90 days prior to screening - Use of any OADs (other than SGLT2i in monotherapy or in combination with metformin or DPP4i or pioglitazone as described in the inclusion criteria) within 90 days prior to the day of screening - Use of glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., exenatide or liraglutide) within 90 days prior to the day of screening - Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent severe metabolic dysregulation (e.g., diabetes ketoacidosis) in the previous 90 days prior to the day of the screening - Subjects presently classified as being in NYHA (New York Heart Association) Class III or IV1 - Renal impairment estimated Glomerular Filtration Rate 60 mL/min/1.73 m2 as per CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) - Impaired liver function, defined as ALT (alanine aminotransferase) equal to or above 2.5 times upper normal limit at screening - Known or suspected hypersensitivity to trial product(s) or related products
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Canada,   Finland,   Hungary,   India,   Russian Federation,   Slovakia,   Slovenia,   Spain,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02773368
Other Study ID Numbers  ICMJE NN9068-4229
2015-001596-48 ( EudraCT Number )
U1111-1168-9343 ( Other Identifier: WHO )
REec-2016-2248 ( Other Identifier: REec )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novo Nordisk A/S
Study Sponsor  ICMJE Novo Nordisk A/S
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
PRS Account Novo Nordisk A/S
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP