Metabolism and Nutrition Disorder, Obesity, Obstructive Sleep Apnoea
Conditions
Keywords
OSA
Brief summary
This trial is conducted in North America. The aim of the trial is to investigate the effect of liraglutide in obese subjects with sleep apnoea.
Interventions
DRUGliraglutide
3.0 mg liraglutide administered subcutaneously (s.c., under the skin) once daily for 32 weeks + diet and exercise
DRUGplacebo
Placebo administered subcutaneously (s.c., under the skin) once daily for 32 weeks + diet and exercise
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent * Body mass index equal to or above 30 kg/m\^2 * Stable body weight (less than 5% self-reported change during the previous 3 months) * Diagnosis of moderate or severe obstructive sleep apnoea (OSA) * Unwilling or unable to use continuous positive airway pressure (CPAP) (or other positive airway pressure) treatment. No CPAP (or other positive airway pressure) treatment for at least four weeks prior to screening * Ability and willingness to comply with all protocol procedures e.g. correct handling of trial product, compliance to visit schedule and dietary advice and complete trial related questionnaires
Exclusion criteria
* Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 inhibitors or insulin within the last 3 months prior to screening * Diagnosis of type 1 or type 2 diabetes per judgement of the investigator * Glycosylated haemoglobin (HbA1c) equal to or above 6.5% * Significant craniofacial abnormalities that may cause OSA * Respiratory and neuromuscular diseases that could interfere with the results of the trial in the opinion of the investigator * Use of central stimulants, hypnotics, mirtazepine, opioids, trazodone within the previous 3 months prior to screening * Obesity induced by drug treatment * Treatment with pramlintide, sibutramine, orlistat, zonisamide, topiramate or phenteremine within the last 3 month prior to screening * Previous surgical treatment for obesity * Screening calcitonin equal to or above 50 ng/L * Familial or personal history of Multiple Endocrine Neoplasia type 2 or familial Medullary Thyroid Carcinoma * Personal history of non-familial Medullary Thyroid Carcinoma * History of chronic pancreatitis or idiopathic acute pancreatitis * History of Major Depressive Disorder or suicide attempts * Systolic blood pressure equal to or above 160 mmHg and/or diastolic blood pressure equal to or above 100 mmHg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Apnoea-hypopnoea Index (AHI) | Week 0, Week 32 | Observed mean change from baseline in AHI (events/hour) after 32 weeks of treatment. AHI (apnoea and hypopnoea events per hour of sleep) is a measure used for the diagnosis and severity classification of obstructive sleep apnoea. AHI severity category: none ≤4.9; mild 5.0-14.9; moderate 15.0-29.9; severe ≥30.0 events/hour. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight (kg) | Week 0, week 32 | Observed mean change from baseline in fasting body weight (kg) after 32 weeks of treatment. |
| Change From Baseline in Fasting Plasma Glucose | Week 0, week 32 | Observed mean change from baseline in fasting plasma glucose (mmol/L) after 32 weeks of treatment. |
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) (%) | Week 0, week 32 | Observed mean change from baseline in glycosylated haemoglobin (HbA1c) (%) after 32 weeks of treatment. |
Countries
Canada, United States
Participant flow
Recruitment details
The trial was conducted at 40 sites in 2 countries, as follows: United States: 35 sites; Canada: 5 sites.
Pre-assignment details
The trial consisted of a 2-week screening period before randomisation.
Participants by arm
| Arm | Count |
|---|---|
| Liraglutide 3.0 mg Subjects were administered 3.0 mg of liraglutide subcutaneously (s.c., under the skin) once daily for 32 weeks. Subjects were also prescribed a 500 kcal/day-deficit diet and exercise for a minimum of 150 min/week. | 180 |
| Placebo Subjects were administered placebo subcutaneously (s.c., under the skin) once daily for 32 weeks. Subjects were also prescribed a 500 kcal/day-deficit diet and exercise for a minimum of 150 min/week. | 179 |
| Total | 359 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 20 | 6 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Protocol Violation | 8 | 5 |
| Overall Study | Psychiatric disorder | 1 | 0 |
| Overall Study | Target dose not tolerated | 1 | 0 |
| Overall Study | Unclassified | 2 | 5 |
| Overall Study | Withdrawn consent | 12 | 20 |
Baseline characteristics
| Characteristic | Liraglutide 3.0 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 48.6 years STANDARD_DEVIATION 9.9 | 48.4 years STANDARD_DEVIATION 9.5 | 48.5 years STANDARD_DEVIATION 9.7 |
| Apnoea-hypopnoea index (AHI) | 49.0 events/hour STANDARD_DEVIATION 27.5 | 49.3 events/hour STANDARD_DEVIATION 27.5 | 49.2 events/hour STANDARD_DEVIATION 27.4 |
| Body mass index (BMI) | 38.9 kg/m^2 STANDARD_DEVIATION 6.4 | 39.4 kg/m^2 STANDARD_DEVIATION 7.4 | 39.1 kg/m^2 STANDARD_DEVIATION 6.9 |
| Body weight | 116.5 kg STANDARD_DEVIATION 23 | 118.7 kg STANDARD_DEVIATION 25.4 | 117.6 kg STANDARD_DEVIATION 24.2 |
| Fasting plasma glucose (FPG) | 5.4 mmol/L STANDARD_DEVIATION 0.6 | 5.4 mmol/L STANDARD_DEVIATION 0.9 | 5.4 mmol/L STANDARD_DEVIATION 0.8 |
| Glycosylated haemoglobin (HbA1c) | 5.7 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.4 | 5.6 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.4 | 5.7 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.4 |
| Sex: Female, Male Female | 51 Participants | 50 Participants | 101 Participants |
| Sex: Female, Male Male | 129 Participants | 129 Participants | 258 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 117 / 176 | 84 / 179 |
| serious Total, serious adverse events | 6 / 176 | 6 / 179 |
Outcome results
Primary
Change From Baseline in Apnoea-hypopnoea Index (AHI)
Observed mean change from baseline in AHI (events/hour) after 32 weeks of treatment. AHI (apnoea and hypopnoea events per hour of sleep) is a measure used for the diagnosis and severity classification of obstructive sleep apnoea. AHI severity category: none ≤4.9; mild 5.0-14.9; moderate 15.0-29.9; severe ≥30.0 events/hour.
Time frame: Week 0, Week 32
Population: Full analysis set (FAS) - included all randomised subjects. 334 subjects contributed to the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Apnoea-hypopnoea Index (AHI) | -12.22 events/hour | Standard Deviation 23.34 |
| Placebo | Change From Baseline in Apnoea-hypopnoea Index (AHI) | -6.08 events/hour | Standard Deviation 25.9 |
Comparison: Let μ liraglutide 3.0mg and μ placebo denote mean change in AHI for liraglutide 3.0 mg and placebo,respectively. The null-hypothesis and the alternative was H0: μliraglutide 3.0mg = μplacebo against the alternative HA: μliraglutide 3.0mg ≠ μplacebo.p-value: 0.01595% CI: [-11, -1.19]ANCOVA
Secondary
Change From Baseline in Body Weight (kg)
Observed mean change from baseline in fasting body weight (kg) after 32 weeks of treatment.
Time frame: Week 0, week 32
Population: Full analysis set (FAS) - included all randomised subjects. 353 subjects contributed to the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Body Weight (kg) | -6.73 kg | Standard Deviation 6.59 |
| Placebo | Change From Baseline in Body Weight (kg) | -1.87 kg | Standard Deviation 5.44 |
Secondary
Change From Baseline in Fasting Plasma Glucose
Observed mean change from baseline in fasting plasma glucose (mmol/L) after 32 weeks of treatment.
Time frame: Week 0, week 32
Population: Full analysis set (FAS) - included all randomised subjects. 355 subjects contributed to the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Fasting Plasma Glucose | -0.15 mmol/L | Standard Deviation 0.69 |
| Placebo | Change From Baseline in Fasting Plasma Glucose | 0.17 mmol/L | Standard Deviation 0.96 |
Secondary
Change From Baseline in Glycosylated Haemoglobin (HbA1c) (%)
Observed mean change from baseline in glycosylated haemoglobin (HbA1c) (%) after 32 weeks of treatment.
Time frame: Week 0, week 32
Population: Full analysis set (FAS) - included all randomised subjects. 345 subjects contributed to the statistical analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Glycosylated Haemoglobin (HbA1c) (%) | -0.36 percentage of glycosylated haemoglobin | Standard Deviation 0.3 |
| Placebo | Change From Baseline in Glycosylated Haemoglobin (HbA1c) (%) | -0.17 percentage of glycosylated haemoglobin | Standard Deviation 0.29 |