A Randomised Controlled Clinical Trial in Type 2 Diabetes Comparing Semaglutide to Placebo and Liraglutide
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| ClinicalTrials.gov Identifier: NCT00696657 |
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Recruitment Status :
Completed
First Posted : June 13, 2008
Results First Posted : September 12, 2018
Last Update Posted : August 14, 2019
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Sponsor:
Novo Nordisk A/S
Information provided by (Responsible Party):
Novo Nordisk A/S
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Brief Summary:
This trial was conducted in Europe,Asia and Africa. Study participants were randomised evenly to treatment with semaglutide (0.1 mg QW - 1.6 mg QW, 6 treatment arms, placebo or liraglutide (1.2 mg QD, or 1.8 mg QD).Treatment allocation to semaglutide or placebo was double-blind, whereas liraglutide treatment was administered open-label.Primary efficacy parameter was HbA1c and the treatment duration was 12 weeks.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Diabetes Diabetes Mellitus, Type 2 | Drug: semaglutide Drug: placebo Drug: liraglutide | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 415 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Investigation of Safety and Efficacy of Five Doses of Semaglutide Versus Placebo and Open-label Liraglutide, as Add on Therapy, in Subjects Diagnosed With Type 2 Diabetes Currently Treated With Metformin or Controlled With Diet and Exercise A 12 Week Multi-centre, Multi National, Double-blind, Placebo-controlled, Randomised, Nine Armed Parallel Group, Dose Finding Trial |
| Actual Study Start Date : | June 3, 2008 |
| Actual Primary Completion Date : | February 5, 2009 |
| Actual Study Completion Date : | February 5, 2009 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Type 2 diabetes
| Arm | Intervention/treatment |
|---|---|
| Experimental: A |
Drug: semaglutide
0.1 mg, once weekly, s.c. injection
Other Name: NN9535 |
| Experimental: B |
Drug: semaglutide
0.2 mg, once weekly, s.c. injection
Other Name: NN9535 |
| Experimental: C |
Drug: semaglutide
0.4 mg, once weekly, s.c. injection
Other Name: NN9535 |
| Experimental: D |
Drug: semaglutide
0.8 mg, once weekly, s.c. injection
Other Name: NN9535 |
| Experimental: E |
Drug: semaglutide
0.8 mg with titration, once weekly, s.c. injection
Other Name: NN9535 |
| Experimental: F |
Drug: semaglutide
1.6 mg with titration, once weekly, s.c. injection
Other Name: NN9535 |
| Placebo Comparator: G1 |
Drug: placebo
0.1 mg, once weekly, s.c. injection |
| Placebo Comparator: G2 |
Drug: placebo
0.2 mg, once weekly, s.c. injection |
| Placebo Comparator: G3 |
Drug: placebo
0.4 mg, once weekly, s.c. injection |
| Placebo Comparator: G4 |
Drug: placebo
0.8 mg with titration, once weekly, s.c. injection |
| Placebo Comparator: G5 |
Drug: placebo
0.8 mg with titration, once weekly, s.c. injection |
| Placebo Comparator: G6 |
Drug: placebo
1.6 mg, once weekly, s.c. injection |
| Experimental: H |
Drug: liraglutide
1.2 mg with titration, once daily, s.c. injection |
| Experimental: I |
Drug: liraglutide
1.8 mg with titration, once daily, s.c. injection |
Primary Outcome Measures :
- HbA1c [ Time Frame: After 12 weeks of treatment. ]Change from baseline in HbA1c was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the last observation carried forward (LOCF) approach.
Secondary Outcome Measures :
- Percentage of Subjects With an Adverse Events [ Time Frame: After 12 weeks of treatment. ]The results of adverse event presented here are treatment emergent, i.e., TEAE. A TEAE was defined as an event that had onset on or after the first date (week 0) on trial product and no later than 5 weeks after the last date on trial product (week 17), or that had onset before the first date on trial product and increases in severity during the treatment period until 5 weeks after the last date on trial product.
- Percentage of Subjects With Hypoglycaemic Episode [ Time Frame: After 12 weeks of treatment ]The results of hypoglycaemic episode presented here are treatment emergent. Hypoglycaemic episodes were defined as treatment emergent if they had onset on or after the first day of randomised treatment (in week 0) and no later than 5 weeks after the last date on trial product (week 17). Hypoglycaemic episodes are classified as follows: Major: If the subject was not able to treat himself or herself and was needed to be administered food, glucagon or intravenous (i.v.) glucose by another person. Minor: If the subject was able to treat himself or herself and measured plasma glucose was <3.1 mmol/L (56 mg/dL). Symptoms only: If the subject was able to treat himself or herself and measured plasma glucose was >=3.1 mmol/L (56 mg/dL) or no plasma glucose measurement was done.
- Change From Baseline in ECG [ Time Frame: Week 0, week 12. ]A standard 12 lead electrocardiogram (ECG) with a 10-second rhythm strip was performed at screening (week -2) and at the end of treatment (week 12). The time frame should be read as "week -2, week 12". Change from baseline in ECG was measured in terms of number of subjects in each category (normal, abnormal, not clinically significant [NCS] or abnormal clinically significant [CS]) at week -2 and week 12 (i.e., change in each category in terms of number of subjects from week -2 to week 12).
- Change From Baseline in Vital Signs (Pulse) [ Time Frame: Week 0, week 12 ]Change from baseline in pulse was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Vital Signs (Blood Pressure; SBP) [ Time Frame: Week 0, week 12 ]Change from baseline in systolic blood pressure (SBP) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Vital Signs (Blood Pressure; DBP) [ Time Frame: Week 0, week 12 ]Change from baseline in diastolic blood pressure (DBP) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Basophils) [ Time Frame: Week 0, week 12 ]Change from baseline in basophils was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Eosinophils) [ Time Frame: Week 0, week 12 ]Change from baseline in eosinophils was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Haematocrit) [ Time Frame: Week 0, week 12 ]Change from baseline in haematocrit (the proportion of blood that consists of red blood cells) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Haemoglobin) [ Time Frame: Week 0, week 12 ]Change from baseline in haemoglobin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Lymphocytes) [ Time Frame: Week 0, week 12 ]Change from baseline in lymphocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Monocytes) [ Time Frame: Week 0, week 12 ]Change from baseline in monocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Neutrophils) [ Time Frame: Week 0, week 12 ]Change from baseline in neutrophils was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Thrombocytes) [ Time Frame: Week 0, week 12 ]Change from baseline in thrombocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Erythrocytes) [ Time Frame: Week 0, week 12 ]Change from baseline in erythrocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Leukocytes) [ Time Frame: Week 0, week 12 ]Change from baseline in leukocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Albumin) [ Time Frame: Week 0, week 12. ]Change from baseline in albumin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Alkaline Phosphatase) [ Time Frame: Week 0, week 12. ]Change from baseline in alkaline phosphatase was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; AST) [ Time Frame: Week 0, week 12. ]Change from baseline in aspartate aminotransferase (AST) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; ALAT) [ Time Frame: Week 0, week 12. ]Change from baseline in alanine aminotransferase (ALAT) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Total Bilirubin) [ Time Frame: Week 0, week 12. ]Change from baseline in total bilirubin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Calcium, Total) [ Time Frame: Week 0, week 12. ]Change from baseline in calcium, total was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Calcium, Ionised) [ Time Frame: Week 0, week 12. ]Change from baseline in calcium, ionised was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Creatinine) [ Time Frame: Week 0, week 12. ]Change from baseline in creatinine was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Potassium) [ Time Frame: Week 0, week 12. ]Change from baseline in potassium was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Sodium) [ Time Frame: Week 0, week 12. ]Change from baseline in sodium was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Urea) [ Time Frame: Week 0, week 12. ]Change from baseline in urea was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Glucose) [ Time Frame: Week 0, week 12 ]Change from baseline in urine-glucose was measured in terms of number of subjects in each category (negative, positive, >=55 mmol/L, or missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).
- Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Haemoglobin) [ Time Frame: Week 0, week 12 ]Change from baseline in urine-haemoglobin was measured in terms of number of subjects in each category (negative, trace, small, moderate/large and missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).
- Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Ketones) [ Time Frame: Week 0, week 12 ]Change from baseline in urine-ketone was measured in terms of number of subjects in each category (negative, positive, >=55 mmol/L and missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).
- Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; pH) [ Time Frame: Week 0, week 12 ]Change from baseline in urine-pH was measured in terms of number of subjects in each category (pH=6.0, 6.5, 7.0, 7.5, 8.0, >=8.5 and missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).
- Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Protein) [ Time Frame: Week 0, week 12 ]Change from baseline in urine-protein was measured in terms of number of subjects in each category at week 0 (negative, 0.3 g/L, 1.0 g/L and missing) and week 12 (negative, trace, 0.3 g/L, 1.0 g/L, >=3.0 g/L and missing). i.e., change in each category in terms of number of subjects from week 0 to week 12.
- Change From Baseline in Calcitonin [ Time Frame: Week 0, week 12. ]Change from baseline in calcitonin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
- Percentage of Subjects Developing Anti-semaglutide Antibodies [ Time Frame: After 12 weeks of treatment ]Antibodies were measured after 12-week of treatment at week 17; percentage of participants with positive anti-semaglutide antibodies are presented here. Assessments of antibodies were not done for subjects allocated to the open-label liraglutide treatment arms.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Men and women-not-of-childbearing potential diagnosed with type 2 diabetes for at least three months
- Stable treatment regimen with either metformin (at least 1500 mg) or diet and exercise alone for at least three months
- HbA1c: 7.0-10.0 % (both inclusive)
- Body weight between 60 kg and 110 kg
Exclusion Criteria:
- Treatment with insulin, GLP-1 receptor agonists (including liraglutide), dipeptidyl peptidase-4 inhibitors, sulphonylurea, thiazolidinediones, Alpha-GIs, or any investigational drug, within the last three months
- Impaired liver or kidney function
- Proliferative retinopathy or maculopathy requiring acute treatment
- Clinically significant active cardiovascular disease and uncontrolled treated/untreated hypertension
- Recurrent major hypoglycaemia or hypoglycaemic unawareness
- Present or planned use of any drug which could interfere with the glucose levels (e.g. systemic corticosteroids)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00696657
Locations
Show 77 study locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
| Study Director: | Global Clinical Registry B. (GCR, 1452), MD, PhD | Novo Nordisk A/S |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novo Nordisk A/S |
| ClinicalTrials.gov Identifier: | NCT00696657 |
| Other Study ID Numbers: |
NN9535-1821 2007-003956-12 ( EudraCT Number ) |
| First Posted: | June 13, 2008 Key Record Dates |
| Results First Posted: | September 12, 2018 |
| Last Update Posted: | August 14, 2019 |
| Last Verified: | July 2019 |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Liraglutide |
Hypoglycemic Agents Physiological Effects of Drugs Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |