Diabetes Mellitus, Type 2, Peripheral Arterial Disease
Conditions
Brief summary
This study is done to see if semaglutide has an effect on walking ability compared with placebo (dummy medicine) in people with peripheral arterial disease (PAD) and type 2 diabetes. Participants will either get semaglutide or placebo ("dummy") medicine - which treatment participants get is decided by chance. Semaglutide is a medicine for type 2 diabetes that can be prescribed by doctors in some countries. Participants will get the study medicine (semaglutide or placebo) in a pre-filled pen for injection. Participants must inject it once a week into the stomach area, thigh, or upper arm, at any time of the day. The study will last for about 59 weeks. Participants will have 8 clinic visits and 1 phone call with the study doctor. At some clinic visits, participants will have blood tests. At some visits participants will also do a treadmill test to measure how far they can walk. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.
Interventions
DRUGSemaglutide
Semaglutide is administered subcutaneously (s.c.; under the skin) once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.
DRUGPlacebo (semaglutide)
Placebo (semaglutide) is administered s.c. once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, age above or equal to 18 years at the time of signing informed consent. For Japan: Male or female, age above or equal to 20 years at time of signing informed consent * Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening. * Symptomatic PAD with intermittent claudication corresponding to Fontaine stage IIa (Rutherford classification grade I, category 1 and 2) meeting all of the following: 1. Stable symptoms of PAD with intermittent claudication in Fontaine stage IIa (able to walk without stopping more than 200 m/656 feet/2 blocks) for at least 90 days prior to the day of screening based on patient interview. 2. Screening flat treadmill test (3.2 km/h (2 mph)): Pain-free walking distance of at least 200 meters/656 feet. 3. Screening constant load treadmill test with fixed inclination of 12% and a fixed speed of 3.2 km/h (2 mph): Walking distance equal to or less than 600 meters/1968 feet. 4. Ankle-brachial-index (ABI) equal to or below 0.90 or toe-brachial index (TBI) equal to or below 0.7 (the leg with lowest index is chosen in case of bilateral disease).
Exclusion criteria
* Current or previous treatment with any GLP-1 receptor agonist (GLP-1-RA) within 90 days prior to the day of screening. * Walking ability limited by conditions other than PAD (e.g. aortic aneurism, dysregulated arrhythmia or hypertension, angina pectoris, heart failure, chronic obstructive or restrictive pulmonary disease, Parkinson's disease, severe peripheral neuropathy, amputations, wheel chair or walker dependency, osteoarthritis, morbid obesity, severe varicose veins, etc.). * Planned orthopaedic surgery in the legs, or other major surgery known on the day of screening (surgery affecting walking ability). * Vascular revascularisation procedure of any kind 180 days prior to the day of screening. * Planned arterial revascularisation known on the day of screening. * Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischemic attack within 180 days prior to the day of screening. * Heart failure presently classified as being in New York Heart Association (NYHA) class III-IV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Maximum Walking Distance on a Constant Load Treadmill Test | Baseline (week 0), end of treatment (week 52) | Change in maximum walking distance on a constant load treadmill test is presented. The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph) and fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants continue on the treadmill after indicating onset of pain and should continue as long as possible until pain limits further activity. This distance is noted as the maximum walking distance. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Follow-up Change in Maximum Walking Distance on a Constant Load Treadmill Test | Baseline (week 0), end of follow-up (week 57) | Change in maximum walking distance on a constant load treadmill test is presented. The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph) and fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants continue on the treadmill after indicating onset of pain and should continue as long as possible until pain limits further activity. This distance is noted as the maximum walking distance. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, which-ever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death. |
| Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) Score | Baseline (week 0), end of treatment (week 52) | Change in VascuQoL-6 score is presented. VascuQoL-6 is a peripheral artery disease-specific questionnaire with 6 items covering social, emotional, functional as well as pain- and symptom-related aspects of the patient´s overall quality of life. Each item has a 4-point response scale (where 1 = worst score and 4 = best score). The endpoint analysed is the total score (range: 6-24) generated by summing the scores from all items. A higher score indicates better health status. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death. |
| Change in Pain-free Walking Distance on a Constant Load Treadmill Test | Baseline (week 0), end of treatment (week 52) | Change in pain-free walking distance on a constant load treadmill test is presented. The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph) and fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants are instructed to when pain starts in either leg and to continue on the treadmill without stopping at this stage. The distance walked is noted as the pain-free walking distance. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death. |
| Follow-up Change in Pain-free Walking Distance on a Constant Load Treadmill Test | Baseline (week 0), end of follow-up (week 57) | Change in pain-free walking distance on a constant load treadmill test is presented. The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph) and fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants are instructed to when pain starts in either leg and to continue on the treadmill without stop-ping at this stage. The distance walked is noted as the pain-free walking distance. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death. |
| Change in Glycosylated Haemoglobin (HbA1c) | Baseline (week 0), end of treatment (week 52) | Change in HbA1c from baseline to week 52 in percentage-point is presented. The outcome measure is evaluated based on the on treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in Body Weight | Baseline (week 0), end of treatment (week 52) | Change in body weight from baseline to week 52 in kilogram (kg) is presented. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in Systolic Blood Pressure | Baseline (week 0), end of treatment (week 52) | Change in systolic blood pressure from baseline to week 52 is presented.The outcome measure is evaluated based on the on treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in Total Cholesterol | Baseline (week 0), end of treatment (week 52) | Change in total cholesterol from baseline to week 52 is presented as ratio to baseline. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in Low-density Lipoprotein (LDL)-Cholesterol | Baseline (week 0), end of treatment (week 52) | Change in LDL-cholesterol from baseline to week 52 is presented as ratio to baseline. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in High Density Lipoprotein (HDL)-Cholesterol | Baseline (week 0), end of treatment (week 52) | Change in HDL-cholesterol from baseline to week 52 is presented as ratio to baseline. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in Triglycerides | Baseline (week 0), end of treatment (week 52) | Change in Triglycerides from baseline to week 52 is presented as ratio to baseline. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in Ankle-Brachial Index (ABI) | Screening (week -2), end of treatment (week 52) | Change in ABI from baseline to week 52 is presented. ABI is calculated as a ratio of the higher ankle systolic pressure to the higher systolic pressure measured in both arms. ABI is measured at both left and right leg and the analysis endpoint is defined as the lower of the two indices. An ABI between 1.0 to 1.4 is considered the normal range. An ABI between 0.90 to 0.99 is considered borderline. An ABI less than 0.90 indicates peripheral artery disease (PAD). The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in Toe-Brachial Index (TBI) | Screening (week -2), end of treatment (week 52) | Change in TBI from baseline to week 52 is presented. TBI is calculated as a ratio of the toe systolic pressure to the higher systolic pressure measured in both arms. TBI is measured at both left and right leg and the analysis endpoint is defined as the lower of the two indices. A TBI range of above or equal to 0.7 is considered normal, whereas a TBI less than 0.7 is considered abnormal. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in Walking Impairment Questionnaire (WIQ) Global Score | Baseline (week 0), end of treatment (week 52) | Change in WIQ global score from baseline to week 52 is presented. WIQ consists of three domains, speed, distance, and stair climbing, consisting of in total 14 questions. Each response is weighted based on the difficulty of the task. Domain scores are determined by dividing the weighted answers by the maximum possible weighted score and multiplying by 100. Global score is calculated as the mean of the three domain scores (ranged from 0% to 100%). A global score of 0% represents inabil-ity to perform any of the tasks and 100% represents no difficulty with any of the tasks. Higher scores indicate better walking ability and less impairment. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
| Change in Short Form 36 (SF-36) Physical Functioning Domain | Baseline (week 0), end of treatment (week 52) | Change in SF-36 physical functioning domain from baseline to week 52 is presented. SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2 (acute version) questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). The 0-100 scale scores from the SF-36 were converted to norm-based scores (Range: 19.03 to 57.60) to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A positive change score indicates an improvement in participant health stats. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). |
Countries
Austria, Belgium, Canada, China, Czechia, Denmark, Germany, Greece, Hungary, India, Japan, Latvia, Malaysia, Norway, Poland, Russia, Spain, Sweden, Taiwan, Thailand, United States
Contacts
STUDY_DIRECTORClinical Transparency (1452)
Novo Nordisk A/S
Participant flow
Recruitment details
The trial was conducted at 129 sites in 21 countries.
Pre-assignment details
Participants were randomized in a 1:1 ratio to receive treatment with either semaglutide or placebo as an adjunct to standard-of-care.
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide Participants received once-weekly (OW) subcutaneous injection (s. c.) of semaglutide for 52 weeks. Participants received a dose of 0.25 milligrams (mg) from week 0 to week 4, then the dose was increased to 0.5 mg from week 4 to week 8. From week 8 to week 52, the dosage was 1.0 mg. | 396 |
| Placebo Participants received once-weekly (OW) subcutaneous injection (s. c.) of placebo matched for semaglutide for 52 weeks. | 396 |
| Total | 792 |
Baseline characteristics
| Characteristic | Placebo | Total | Semaglutide |
|---|---|---|---|
| Age, Continuous | 67.0 Years STANDARD_DEVIATION 8.96 | 66.6 Years STANDARD_DEVIATION 9.35 | 66.2 Years STANDARD_DEVIATION 9.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 13 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 385 Participants | 773 Participants | 388 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 6 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 109 Participants | 240 Participants | 131 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 279 Participants | 538 Participants | 259 Participants |
| Sex: Female, Male Female | 88 Participants | 195 Participants | 107 Participants |
| Sex: Female, Male Male | 308 Participants | 597 Participants | 289 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 396 | 9 / 395 |
| other Total, other adverse events | 47 / 396 | 24 / 395 |
| serious Total, serious adverse events | 74 / 396 | 78 / 395 |
Outcome results
Primary
Change in Maximum Walking Distance on a Constant Load Treadmill Test
Change in maximum walking distance on a constant load treadmill test is presented. The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph) and fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants continue on the treadmill after indicating onset of pain and should continue as long as possible until pain limits further activity. This distance is noted as the maximum walking distance. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Semaglutide | Change in Maximum Walking Distance on a Constant Load Treadmill Test | 1.21 Ratio of maximum walking distance |
| Placebo | Change in Maximum Walking Distance on a Constant Load Treadmill Test | 1.08 Ratio of maximum walking distance |
p-value: 0.000495% CI: [1.056, 1.211]Wilcoxon (Mann-Whitney)
Secondary
Change in Ankle-Brachial Index (ABI)
Change in ABI from baseline to week 52 is presented. ABI is calculated as a ratio of the higher ankle systolic pressure to the higher systolic pressure measured in both arms. ABI is measured at both left and right leg and the analysis endpoint is defined as the lower of the two indices. An ABI between 1.0 to 1.4 is considered the normal range. An ABI between 0.90 to 0.99 is considered borderline. An ABI less than 0.90 indicates peripheral artery disease (PAD). The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Screening (week -2), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Ankle-Brachial Index (ABI) | 1.06 Ratio of ABI | Geometric Coefficient of Variation 34 |
| Placebo | Change in Ankle-Brachial Index (ABI) | 1.02 Ratio of ABI | Geometric Coefficient of Variation 19.6 |
Secondary
Change in Body Weight
Change in body weight from baseline to week 52 in kilogram (kg) is presented. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Body Weight | -5.2 Kilogram (kg) | Standard Deviation 4.8 |
| Placebo | Change in Body Weight | -1.2 Kilogram (kg) | Standard Deviation 4.2 |
Secondary
Change in Glycosylated Haemoglobin (HbA1c)
Change in HbA1c from baseline to week 52 in percentage-point is presented. The outcome measure is evaluated based on the on treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Glycosylated Haemoglobin (HbA1c) | -0.8 Percentage-point of HbA1c | Standard Deviation 1.1 |
| Placebo | Change in Glycosylated Haemoglobin (HbA1c) | 0.2 Percentage-point of HbA1c | Standard Deviation 1.1 |
Secondary
Change in High Density Lipoprotein (HDL)-Cholesterol
Change in HDL-cholesterol from baseline to week 52 is presented as ratio to baseline. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in High Density Lipoprotein (HDL)-Cholesterol | 1.04 Ratio of HDL | Geometric Coefficient of Variation 15.95 |
| Placebo | Change in High Density Lipoprotein (HDL)-Cholesterol | 0.99 Ratio of HDL | Geometric Coefficient of Variation 13.91 |
Secondary
Change in Low-density Lipoprotein (LDL)-Cholesterol
Change in LDL-cholesterol from baseline to week 52 is presented as ratio to baseline. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Low-density Lipoprotein (LDL)-Cholesterol | 0.99 Ratio of LDL | Geometric Coefficient of Variation 38.37 |
| Placebo | Change in Low-density Lipoprotein (LDL)-Cholesterol | 1.03 Ratio of LDL | Geometric Coefficient of Variation 42.27 |
Secondary
Change in Pain-free Walking Distance on a Constant Load Treadmill Test
Change in pain-free walking distance on a constant load treadmill test is presented. The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph) and fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants are instructed to when pain starts in either leg and to continue on the treadmill without stopping at this stage. The distance walked is noted as the pain-free walking distance. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Semaglutide | Change in Pain-free Walking Distance on a Constant Load Treadmill Test | 1.21 Ratio of pain-free walking distance |
| Placebo | Change in Pain-free Walking Distance on a Constant Load Treadmill Test | 1.10 Ratio of pain-free walking distance |
p-value: 0.004695% CI: [1.033, 1.197]Wilcoxon (Mann-Whitney)
Secondary
Change in Short Form 36 (SF-36) Physical Functioning Domain
Change in SF-36 physical functioning domain from baseline to week 52 is presented. SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2 (acute version) questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). The 0-100 scale scores from the SF-36 were converted to norm-based scores (Range: 19.03 to 57.60) to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A positive change score indicates an improvement in participant health stats. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Short Form 36 (SF-36) Physical Functioning Domain | 2.98 Scores on a scale | Standard Deviation 7.32 |
| Placebo | Change in Short Form 36 (SF-36) Physical Functioning Domain | 1.52 Scores on a scale | Standard Deviation 7.17 |
Secondary
Change in Systolic Blood Pressure
Change in systolic blood pressure from baseline to week 52 is presented.The outcome measure is evaluated based on the on treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Systolic Blood Pressure | -4 Millimetre of mercury (mmHg) | Standard Deviation 15 |
| Placebo | Change in Systolic Blood Pressure | -1 Millimetre of mercury (mmHg) | Standard Deviation 18 |
Secondary
Change in Toe-Brachial Index (TBI)
Change in TBI from baseline to week 52 is presented. TBI is calculated as a ratio of the toe systolic pressure to the higher systolic pressure measured in both arms. TBI is measured at both left and right leg and the analysis endpoint is defined as the lower of the two indices. A TBI range of above or equal to 0.7 is considered normal, whereas a TBI less than 0.7 is considered abnormal. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Screening (week -2), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Toe-Brachial Index (TBI) | 1.07 Ratio of TBI | Geometric Coefficient of Variation 34.4 |
| Placebo | Change in Toe-Brachial Index (TBI) | 1.04 Ratio of TBI | Geometric Coefficient of Variation 37.3 |
Secondary
Change in Total Cholesterol
Change in total cholesterol from baseline to week 52 is presented as ratio to baseline. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Total Cholesterol | 0.96 Ratio of total cholesterol | Geometric Coefficient of Variation 20.18 |
| Placebo | Change in Total Cholesterol | 1.00 Ratio of total cholesterol | Geometric Coefficient of Variation 19.88 |
Secondary
Change in Triglycerides
Change in Triglycerides from baseline to week 52 is presented as ratio to baseline. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Triglycerides | 0.80 Ratio of triglycerides | Geometric Coefficient of Variation 45.95 |
| Placebo | Change in Triglycerides | 0.95 Ratio of triglycerides | Geometric Coefficient of Variation 41.73 |
Secondary
Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) Score
Change in VascuQoL-6 score is presented. VascuQoL-6 is a peripheral artery disease-specific questionnaire with 6 items covering social, emotional, functional as well as pain- and symptom-related aspects of the patient´s overall quality of life. Each item has a 4-point response scale (where 1 = worst score and 4 = best score). The endpoint analysed is the total score (range: 6-24) generated by summing the scores from all items. A higher score indicates better health status. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Semaglutide | Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) Score | 2.0 Scores on a scale |
| Placebo | Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) Score | 1.0 Scores on a scale |
p-value: 0.010895% CI: [0.478, 1.518]Wilcoxon (Mann-Whitney)
Secondary
Change in Walking Impairment Questionnaire (WIQ) Global Score
Change in WIQ global score from baseline to week 52 is presented. WIQ consists of three domains, speed, distance, and stair climbing, consisting of in total 14 questions. Each response is weighted based on the difficulty of the task. Domain scores are determined by dividing the weighted answers by the maximum possible weighted score and multiplying by 100. Global score is calculated as the mean of the three domain scores (ranged from 0% to 100%). A global score of 0% represents inabil-ity to perform any of the tasks and 100% represents no difficulty with any of the tasks. Higher scores indicate better walking ability and less impairment. The outcome measure is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure).
Time frame: Baseline (week 0), end of treatment (week 52)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Walking Impairment Questionnaire (WIQ) Global Score | 9.48 %-point scores on a scale | Standard Deviation 18.63 |
| Placebo | Change in Walking Impairment Questionnaire (WIQ) Global Score | 6.51 %-point scores on a scale | Standard Deviation 20.53 |
Secondary
Follow-up Change in Maximum Walking Distance on a Constant Load Treadmill Test
Change in maximum walking distance on a constant load treadmill test is presented. The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph) and fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants continue on the treadmill after indicating onset of pain and should continue as long as possible until pain limits further activity. This distance is noted as the maximum walking distance. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, which-ever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Time frame: Baseline (week 0), end of follow-up (week 57)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Semaglutide | Follow-up Change in Maximum Walking Distance on a Constant Load Treadmill Test | 1.16 Ratio of maximum walking distance |
| Placebo | Follow-up Change in Maximum Walking Distance on a Constant Load Treadmill Test | 1.10 Ratio of maximum walking distance |
p-value: 0.03895% CI: [1.004, 1.156]Wilcoxon (Mann-Whitney)
Secondary
Follow-up Change in Pain-free Walking Distance on a Constant Load Treadmill Test
Change in pain-free walking distance on a constant load treadmill test is presented. The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph) and fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants are instructed to when pain starts in either leg and to continue on the treadmill without stop-ping at this stage. The distance walked is noted as the pain-free walking distance. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Time frame: Baseline (week 0), end of follow-up (week 57)
Population: Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Semaglutide | Follow-up Change in Pain-free Walking Distance on a Constant Load Treadmill Test | 1.18 Ratio of pain-free walking distance |
| Placebo | Follow-up Change in Pain-free Walking Distance on a Constant Load Treadmill Test | 1.10 Ratio of pain-free walking distance |