Obesity, Obstructive Sleep Apnea
Conditions
Brief summary
The purpose of this study is to evaluate the effect and safety of tirzepatide in participants with moderate to severe obstructive sleep apnea and obesity who are both unwilling or unable to use Positive Airway Pressure (PAP) therapy in GPI1 and those who are and plan to stay on PAP therapy in GPI2.
Interventions
DRUGTirzepatide
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For GPI1 Participants: \- Participants who are unable or unwilling to use PAP therapy. Participants must not have used PAP for at least 4 weeks prior to screening. For GPI2 Participants: \- Have been on PAP therapy for at least 3 consecutive months prior to screening and plan to continue PAP therapy during the study For Both GPI1 and GPI2 Participants: * Have an AHI ≥15 on PSG as part of the trial at screening * Have a body mass index (BMI) ≥30 kilogram/square meter (kg/m²) * Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight
Exclusion criteria
For GPI2 Participants: * Have personal or job-related responsibilities, or in the opinion of the investigator have any situation, that would make it unsafe to stop PAP therapy for 7 days prior to PSG testing during the course of the study * Are unwilling to stop PAP therapy for 7 days prior to polysomnography (PSG) testing during the course of the study For GPI1 and GPI2 Participants: * Female participants must not be pregnant, intending to be pregnant, breastfeeding, or intending to breastfeed. * Have type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), history of ketoacidosis, or hyperosmolar state/coma. * Have HbA1c ≥ 6.5% (≥ 48 mmol/mol) at baseline * Any previous or planned surgery for sleep apnea or major ear, nose or throat surgery, including tonsillectomy and adenoidectomy that still may affect breathing at time of baseline * Have significant craniofacial abnormalities that may affect breathing at baseline * Have diagnosis of Central or Mixed Sleep Apnea with % of mixed or central apneas/hypopneas ≥50%, or diagnosis of Cheyne Stokes Respiration * Diagnosis of Obesity Hypoventilation Syndrome or daytime hypercapnia. * Active device treatment of OSA other than PAP therapy (for example, dental appliance), or other treatment, that in the opinion of the investigator, may interfere with study outcomes, unless willing to stop treatment at baseline and throughout the study. * Respiratory and neuromuscular diseases that could interfere with the results of the trial in the opinion of the investigator. * Have a self-reported change in body weight \>5 kg within 3 months prior to screening * Have a prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty if performed more than 1 year prior to screening) * Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months (for example, mucosal ablation, gastric artery embolization, intragastric balloon, and duodenal-jejunal bypass sleeve)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Apnea-Hypopnea Index (AHI) | Baseline, Week 52 | AHI, Apnea-Hypopnea Index, is the number of apneas or hypopneas recorded via polysomnography during the study per hour of sleep. Apnea is defined as a cessation of airflow lasting at least 10 seconds, hypopnea as a decrease in airflow by at least 30% from baseline for at least 10 seconds occurring with a drop in oxygen saturation (SpO₂) by at least 4%. AHI values are categorized as 5-15 events/hr = mild; 15-\<30 events/hr = moderate; and ≥ 30 events/hr = severe. a significant reduction in values indicates a positive outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Apnea-Hypopnea Index (AHI) | Baseline, Week 52 | Percent Change From Baseline in AHI was evaluated. |
| Percentage of Participants With ≥50% AHI Reduction From Baseline | Week 52 | Percentage of participants achieving ≥50% AHI reduction from baseline to Week 52 was evaluated. |
| Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10 | Week 52 | The percentage of participants with OSA remission (AHI \<5 events per hour of sleep) or with mild OSA without excessive daytime sleepiness (AHI 5-14 events per hour of sleep with ESS ≤10) at Week 52 was evaluated. The ESS is used to assess improvements in excessive daytime sleepiness from baseline to Week 52. The ESS is an 8-item, participant-completed measure that asks the participant to rate, on a scale of 0 (no chance of dozing) to 3 (high chance of dozing), their usual chances of dozing in 8 different daytime situations, with a recall period of in recent times. The ESS total score is the sum of the 8-item scores and ranges from 0 to 24, with higher scores indicating greater daytime sleepiness. |
| Change From Baseline in Systolic Blood Pressure (SBP) | Baseline, Week 48 | Change in systolic blood pressure from baseline to Week 48 was evaluated. |
| Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD) | Baseline, Week 52 | PROMIS SRI consists of 8 items that assess self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours and perceived functional impairments associated with sleep problems. PROMIS SRI has a recall period of in the past 7 days and each item is rated on a 5-point scale from not at all to very much. PROMIS SD consists of 8 items that assess self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. PROMIS SD has a recall period of in the past 7 days and each item is rated on a 5-point scale ranging from not at all to very much, never to always, or very poor to very good. For both PROMIS SRI and PROMIS SD, item responses are used to generate T-scores which are standardized scores with a mean of 50 and a standard deviation of 10 (score range cannot be specified for T-scores). Higher T-scores indicate worse outcomes; more sleep-related impairment (PROMIS SRI) or more sleep disturbance (PROMIS SD). |
| Percent Change From Baseline in Body Weight | Baseline, Week 52 | Percent Change from Baseline in Body Weight was evaluated. |
| Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration | Baseline, Week 52 | HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. |
| Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour) | Baseline, Week 52 | SASHB was determined by measuring the respiratory event-associated area under the curve for oxygen desaturation from pre-event baseline and represents the cumulative burden of intermittent hypoxia caused by OSA-related sleep-disordered breathing at sleep. |
Countries
Australia, Brazil, China, Czechia, Germany, Japan, Mexico, Puerto Rico, Taiwan, United States
Participant flow
Recruitment details
NCT05412004 supports two pivotal studies: I8F-MC-GPI1 (GPI1; Study 1) and I8F-MC-GPI2 (GPI2; Study 2), conducted under the single master protocol I8F-MC-GPIF. The studies were conducted under a single overarching trial structure for operational efficiencies, but the study participants for both studies are different (GPI1 included participants who were unable or unwilling to use positive airway pressure (PAP) therapy, while GPI2 included those on PAP therapy).
Participants by arm
| Arm | Count |
|---|---|
| Tirzepatide MTD_GPI1 Participants not on positive airway pressure (PAP) therapy received a maximum tolerated dose (MTD) of 10 milligrams (mg) or 15 mg of Tirzepatide once weekly (QW) as a subcutaneous (SC) injection for 52 weeks, including the initial dose escalation by 2.5 mg every 4 weeks. | 114 |
| Placebo_GPI1 Participants not on PAP therapy received placebo QW as an SC injection for 52 weeks. | 120 |
| Tirzepatide MTD_GPI2 Participants who are on PAP therapy received an MTD of 10 mg or 15 mg of Tirzepatide QW as an SC injection for 52 weeks, including the initial dose escalation by 2.5 mg every 4 weeks. | 120 |
| Placebo_GPI2 Participants who are on PAP therapy received placebo QW as an SC injection for 52 weeks. | 115 |
| Total | 469 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 1 | 5 |
| Overall Study | Assigned Treatment by Mistake | 5 | 10 | 2 | 5 |
| Overall Study | Lost to Follow-up | 3 | 0 | 0 | 0 |
| Overall Study | Patient could not travel to site | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 |
| Overall Study | Screen Failure | 0 | 0 | 0 | 1 |
| Overall Study | The participant quit treatment and study due to their schedule and the final V801 was done remotely | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 19 | 4 | 14 |
Baseline characteristics
| Characteristic | Total | Tirzepatide MTD_GPI1 | Placebo_GPI1 | Tirzepatide MTD_GPI2 | Placebo_GPI2 |
|---|---|---|---|---|---|
| Age, Customized <50years | 224 Participants | 63 Participants | 62 Participants | 54 Participants | 45 Participants |
| Age, Customized >=50years | 245 Participants | 51 Participants | 58 Participants | 66 Participants | 70 Participants |
| Baseline apnea-hypopnea index (AHI) | 50.49 events per hour STANDARD_DEVIATION 28.98 | 52.86 events per hour STANDARD_DEVIATION 30.5 | 50.13 events per hour STANDARD_DEVIATION 31.47 | 46.08 events per hour STANDARD_DEVIATION 22.35 | 53.10 events per hour STANDARD_DEVIATION 30.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 174 Participants | 51 Participants | 47 Participants | 38 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 290 Participants | 63 Participants | 69 Participants | 82 Participants | 76 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 37 Participants | 9 Participants | 9 Participants | 10 Participants | 9 Participants |
| Race (NIH/OMB) Asian | 80 Participants | 23 Participants | 24 Participants | 17 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 6 Participants | 7 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 325 Participants | 74 Participants | 80 Participants | 85 Participants | 86 Participants |
| Region of Enrollment Australia | 25 Participants | 1 Participants | 5 Participants | 10 Participants | 9 Participants |
| Region of Enrollment Brazil | 84 Participants | 24 Participants | 25 Participants | 18 Participants | 17 Participants |
| Region of Enrollment China | 37 Participants | 14 Participants | 14 Participants | 4 Participants | 5 Participants |
| Region of Enrollment Czechia | 23 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants |
| Region of Enrollment Germany | 46 Participants | 7 Participants | 7 Participants | 16 Participants | 16 Participants |
| Region of Enrollment Japan | 20 Participants | 3 Participants | 4 Participants | 7 Participants | 6 Participants |
| Region of Enrollment Mexico | 69 Participants | 20 Participants | 19 Participants | 14 Participants | 16 Participants |
| Region of Enrollment Taiwan | 16 Participants | 5 Participants | 4 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 149 Participants | 35 Participants | 36 Participants | 41 Participants | 37 Participants |
| Sex: Female, Male Female | 142 Participants | 36 Participants | 41 Participants | 33 Participants | 32 Participants |
| Sex: Female, Male Male | 327 Participants | 78 Participants | 79 Participants | 87 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 114 | 0 / 120 | 0 / 119 | 0 / 114 |
| other Total, other adverse events | 91 / 114 | 91 / 120 | 98 / 119 | 82 / 114 |
| serious Total, serious adverse events | 9 / 114 | 7 / 120 | 7 / 119 | 12 / 114 |
Outcome results
Primary
Change From Baseline in Apnea-Hypopnea Index (AHI)
AHI, Apnea-Hypopnea Index, is the number of apneas or hypopneas recorded via polysomnography during the study per hour of sleep. Apnea is defined as a cessation of airflow lasting at least 10 seconds, hypopnea as a decrease in airflow by at least 30% from baseline for at least 10 seconds occurring with a drop in oxygen saturation (SpO₂) by at least 4%. AHI values are categorized as 5-15 events/hr = mild; 15-\<30 events/hr = moderate; and ≥ 30 events/hr = severe. a significant reduction in values indicates a positive outcome.
Time frame: Baseline, Week 52
Population: Modified intent-to-treat (mITT) population consisting of all randomized participants who are exposed to at least 1 dose of study intervention and have evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tirzepatide MTD_GPI1 | Change From Baseline in Apnea-Hypopnea Index (AHI) | -25.25 events per hour | Standard Error 2.06 |
| Placebo_GPI1 | Change From Baseline in Apnea-Hypopnea Index (AHI) | -5.25 events per hour | Standard Error 2.11 |
| Tirzepatide MTD_GPI2 | Change From Baseline in Apnea-Hypopnea Index (AHI) | -29.27 events per hour | Standard Error 1.99 |
| Placebo_GPI2 | Change From Baseline in Apnea-Hypopnea Index (AHI) | -5.51 events per hour | Standard Error 2.21 |
p-value: <0.00195% CI: [-25.82, -14.2]ANCOVA
p-value: <0.00195% CI: [-29.61, -17.93]ANCOVA
Secondary
Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration
HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment.
Time frame: Baseline, Week 52
Population: mITT population consisting of all randomized participants who are exposed to at least 1 dose of study intervention and have evaluable data for this outcome.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tirzepatide MTD_GPI1 | Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration | -1.42 Milligram per liter (mg/L) | Standard Error 0.151 |
| Placebo_GPI1 | Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration | -0.70 Milligram per liter (mg/L) | Standard Error 0.203 |
| Tirzepatide MTD_GPI2 | Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration | -1.37 Milligram per liter (mg/L) | Standard Error 0.13 |
| Placebo_GPI2 | Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration | -0.33 Milligram per liter (mg/L) | Standard Error 0.236 |
p-value: 0.75295% CI: [-1.21, -0.22]ANCOVA
p-value: 0.3595% CI: [-1.57, -0.51]ANCOVA
Secondary
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD)
PROMIS SRI consists of 8 items that assess self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours and perceived functional impairments associated with sleep problems. PROMIS SRI has a recall period of in the past 7 days and each item is rated on a 5-point scale from not at all to very much. PROMIS SD consists of 8 items that assess self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. PROMIS SD has a recall period of in the past 7 days and each item is rated on a 5-point scale ranging from not at all to very much, never to always, or very poor to very good. For both PROMIS SRI and PROMIS SD, item responses are used to generate T-scores which are standardized scores with a mean of 50 and a standard deviation of 10 (score range cannot be specified for T-scores). Higher T-scores indicate worse outcomes; more sleep-related impairment (PROMIS SRI) or more sleep disturbance (PROMIS SD).
Time frame: Baseline, Week 52
Population: mITT population consisting of all randomized participants who are exposed to at least 1 dose of study intervention and have evaluable data for this outcome.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tirzepatide MTD_GPI1 | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD) | Sleep Disturbance | -4.47 T score | Standard Error 0.69 |
| Tirzepatide MTD_GPI1 | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD) | Sleep-Related Impairment | -6.57 T score | Standard Error 0.83 |
| Placebo_GPI1 | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD) | Sleep-Related Impairment | -3.13 T score | Standard Error 0.8 |
| Placebo_GPI1 | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD) | Sleep Disturbance | -2.44 T score | Standard Error 0.7 |
| Tirzepatide MTD_GPI2 | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD) | Sleep Disturbance | -6.98 T score | Standard Error 0.82 |
| Tirzepatide MTD_GPI2 | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD) | Sleep-Related Impairment | -8.18 T score | Standard Error 0.95 |
| Placebo_GPI2 | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD) | Sleep Disturbance | -3.08 T score | Standard Error 0.88 |
| Placebo_GPI2 | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD) | Sleep-Related Impairment | -3.91 T score | Standard Error 1.03 |
Comparison: Sleep Disturbancep-value: 0.03795% CI: [-3.95, -0.12]ANCOVA
Comparison: Sleep Related Impairmentp-value: 0.00395% CI: [-5.69, -1.17]ANCOVA
Comparison: Sleep Disturbancep-value: <0.00195% CI: [-6.21, -1.58]ANCOVA
Comparison: Sleep-Related Impairmentp-value: 0.00295% CI: [-6.97, -1.56]ANCOVA
Secondary
Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour)
SASHB was determined by measuring the respiratory event-associated area under the curve for oxygen desaturation from pre-event baseline and represents the cumulative burden of intermittent hypoxia caused by OSA-related sleep-disordered breathing at sleep.
Time frame: Baseline, Week 52
Population: mITT population consisting of all randomized participants who are exposed to at least 1 dose of study intervention and have evaluable data for this outcome.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tirzepatide MTD_GPI1 | Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour) | -95.19 %.min/hr | Standard Error 4.081 |
| Placebo_GPI1 | Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour) | -25.07 %.min/hr | Standard Error 9.804 |
| Tirzepatide MTD_GPI2 | Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour) | -102.98 %.min/hr | Standard Error 3.758 |
| Placebo_GPI2 | Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour) | -41.69 %.min/hr | Standard Error 11.313 |
95% CI: [-90.94, -49.31]
95% CI: [-84.66, -37.93]
Secondary
Change From Baseline in Systolic Blood Pressure (SBP)
Change in systolic blood pressure from baseline to Week 48 was evaluated.
Time frame: Baseline, Week 48
Population: mITT population consisting of all randomized participants who are exposed to at least 1 dose of study intervention and have evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tirzepatide MTD_GPI1 | Change From Baseline in Systolic Blood Pressure (SBP) | -9.46 Millimeters of mercury (mm Hg) | Standard Error 1.02 |
| Placebo_GPI1 | Change From Baseline in Systolic Blood Pressure (SBP) | -1.84 Millimeters of mercury (mm Hg) | Standard Error 1.03 |
| Tirzepatide MTD_GPI2 | Change From Baseline in Systolic Blood Pressure (SBP) | -7.64 Millimeters of mercury (mm Hg) | Standard Error 1.03 |
| Placebo_GPI2 | Change From Baseline in Systolic Blood Pressure (SBP) | -3.94 Millimeters of mercury (mm Hg) | Standard Error 1.18 |
p-value: <0.00195% CI: [-10.48, -4.77]ANCOVA
p-value: 0.01795% CI: [-6.75, -0.65]ANCOVA
Secondary
Percentage of Participants With ≥50% AHI Reduction From Baseline
Percentage of participants achieving ≥50% AHI reduction from baseline to Week 52 was evaluated.
Time frame: Week 52
Population: mITT population consisting of all randomized participants who are exposed to at least 1 dose of study intervention and have evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tirzepatide MTD_GPI1 | Percentage of Participants With ≥50% AHI Reduction From Baseline | 61.22 percentage of participants |
| Placebo_GPI1 | Percentage of Participants With ≥50% AHI Reduction From Baseline | 18.96 percentage of participants |
| Tirzepatide MTD_GPI2 | Percentage of Participants With ≥50% AHI Reduction From Baseline | 72.40 percentage of participants |
| Placebo_GPI2 | Percentage of Participants With ≥50% AHI Reduction From Baseline | 23.25 percentage of participants |
p-value: <0.00195% CI: [30.76, 54.79]Regression, Logistic
p-value: <0.00195% CI: [36.55, 60.65]Regression, Logistic
Secondary
Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10
The percentage of participants with OSA remission (AHI \<5 events per hour of sleep) or with mild OSA without excessive daytime sleepiness (AHI 5-14 events per hour of sleep with ESS ≤10) at Week 52 was evaluated. The ESS is used to assess improvements in excessive daytime sleepiness from baseline to Week 52. The ESS is an 8-item, participant-completed measure that asks the participant to rate, on a scale of 0 (no chance of dozing) to 3 (high chance of dozing), their usual chances of dozing in 8 different daytime situations, with a recall period of in recent times. The ESS total score is the sum of the 8-item scores and ranges from 0 to 24, with higher scores indicating greater daytime sleepiness.
Time frame: Week 52
Population: mITT population consisting of all randomized participants who are exposed to at least 1 dose of study intervention and have evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tirzepatide MTD_GPI1 | Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10 | 42.17 percentage of participants |
| Placebo_GPI1 | Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10 | 15.88 percentage of participants |
| Tirzepatide MTD_GPI2 | Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10 | 50.24 percentage of participants |
| Placebo_GPI2 | Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10 | 14.33 percentage of participants |
p-value: <0.00195% CI: [18.27, 39.22]Regression, Logistic
p-value: <0.00195% CI: [22.12, 44.31]Regression, Logistic
Secondary
Percent Change From Baseline in Apnea-Hypopnea Index (AHI)
Percent Change From Baseline in AHI was evaluated.
Time frame: Baseline, Week 52
Population: mITT population consisting of all randomized participants who are exposed to at least 1 dose of study intervention and have evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tirzepatide MTD_GPI1 | Percent Change From Baseline in Apnea-Hypopnea Index (AHI) | -50.68 percentage change | Standard Error 5.9 |
| Placebo_GPI1 | Percent Change From Baseline in Apnea-Hypopnea Index (AHI) | -3.03 percentage change | Standard Error 7.07 |
| Tirzepatide MTD_GPI2 | Percent Change From Baseline in Apnea-Hypopnea Index (AHI) | -58.72 percentage change | Standard Error 5.28 |
| Placebo_GPI2 | Percent Change From Baseline in Apnea-Hypopnea Index (AHI) | -2.50 percentage change | Standard Error 6.95 |
p-value: <0.00195% CI: [-65.76, -29.55]ANCOVA
p-value: <0.00195% CI: [-73.73, -38.7]ANCOVA
Secondary
Percent Change From Baseline in Body Weight
Percent Change from Baseline in Body Weight was evaluated.
Time frame: Baseline, Week 52
Population: mITT population consisting of all randomized participants who are exposed to at least 1 dose of study intervention and have evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tirzepatide MTD_GPI1 | Percent Change From Baseline in Body Weight | -17.65 Percent change | Standard Error 0.69 |
| Placebo_GPI1 | Percent Change From Baseline in Body Weight | -1.56 Percent change | Standard Error 0.68 |
| Tirzepatide MTD_GPI2 | Percent Change From Baseline in Body Weight | -19.62 Percent change | Standard Error 0.71 |
| Placebo_GPI2 | Percent Change From Baseline in Body Weight | -2.34 Percent change | Standard Error 0.74 |
p-value: <0.00195% CI: [-17.99, -14.19]ANCOVA
p-value: <0.00195% CI: [-19.29, -15.28]ANCOVA