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Intervention study of exercise program for type 2 diabetes mellitus

Intervention study of exercise program for type 2 diabetes mellitus

228

Demographics and baseline characteristics were generally balanced between groups. Approximately 60% of patients were male, with a mean age of approximately 55 years. Patients in both groups were overweight with an average BMI of approximately 26-27 kg/m^2 and had average HbA1c levels of approximately 7.7%.

A total of 228 patients were randomized into 2 groups (113 patients to the exercise group and 115 patients to the non-exercise group) comprising the safety analysis set. Of the 228 patients randomized, 3 patients in the exercise group and 1 patient in the non-exercise group were excluded from the FAS. Of the randomized patients, 97 (85.8%) in the exercise group and 108 (93.9%) in the non-exercise group completed the study. The primary reason for discontinuation of the study in the exercise group was adverse events (n=5) and protocol deviation in the non-exercise group (n=2).

The incidence of TEAEs was higher in the exercise group (42.5%) compared with the non-exercise group (29.6%). The most common TEAE was nasopharyngitis (19.5% in the exercise group and 12.2% in the non-exercise group). Musculoskeletal and connective tissue disorders were more common in the exercise group (10.6%) compared with the non-exercise group (5.2%). More patients in the exercise group (2.7%) experienced upper respiratory tract inflammation compared with patients in the non-exercise group (0.9%). Exercise-related TEAEs were reported in 11 (9.7%) patients in the exercise group, which were myalgia (n=4), back pain (n=2), muscle strain, blood pressure decreased, osteoarthritis, dizziness and headache (n=1 each). Of the patients who reported an exercise-related TEAE, 3 (2.7%) patients discontinued the study due to muscle strain, back pain, and osteoarthritis (n=1 each). One patient (0.9%) in the exercise group and 2 patients (1.7%) in the non-exercise group reported a serious TEAE. In the exercise group, head deformity was reported as a serious TEAE in 1 patient. In the non-exercise group, 1 patient reported stress cardiomyopathy and the other patient reported macular degeneration. No exercise-related serious TEAEs were reported. No hypoglycemic events were reported for either group.

The mean (standard deviation) HbA1c level decreased from 7.68% (0.60%) at baseline to 7.37% (0.71%) at Week 13 in the exercise group and increased from 7.71% (0.60%) to 7.76% (0.75%) in the non-exercise group. The mean change from baseline at Week 13 was -0.31% in the exercise group and 0.13% in the non-exercise group. An estimated difference between the 2 groups was -0.44% (95% CI: -0.61, -0.28, p<0.001).

Significantly greater decreases in FBG and glycoalbumin levels were observed in patients in the exercise group compared with the non-exercise group (estimated difference: FBG = -13.0 mg/dL [95% CI: -19.2, -6.7], p<0.001; glycoalbumin = -1.52% [95% CI: -2.10, -0.93], p<0.001), and both parameters increased slightly from baseline to Week 13 in the non-exercise group. Improvement in insulin resistance was observed in patients in the exercise group as shown by decreases in fasting insulin (-0.482 uIU/mL) and HOMA-R (-0.2778); however, the differences between the 2 groups were not statistically significant for either measure at Week 13. HOMA-b was slightly improved in the exercise group at Week 13 (mean change = 0.7340) compared with the non-exercise group (mean change = -1.6589); however, the difference between the 2 groups was not significant.

More patients in the exercise group than the non-exercise group discontinued the study. Exercise group showed a statistically significant improvement over the non-exercise group in primary endpoint, HbA1c. Exercise group showed a statistically significant improvement over non-exercise group in secondary endpoints, FBS and glycoalbumin. No major safety findings were observed in the exercise group. The exercise program appears to be generally well-tolerated.

No

Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas".

https://www.clinicaltrials.jp/file/uOpcIRTbd

Astellas Pharma Inc.

Astellas Pharma Inc.

https://www.astellas.com/jp/ja/contact-us

completed

July. 24, 2018

Interventional

Open label, randomized controlled trial

treatment purpose

N/A

1. Subject has been diagnosed with type 2 diabetes mellitus for at least 12 weeks at informed consent.
2. Subject with hemoglobin A1c (HbA1c) value between 7.0 and 10.0 at screening.
3. Subject with a difference of HbA1c values within +/-1 in past 3 months before screening.
4. Subject with a body mass index (BMI) between 20.0 kg/m2 and 35.0 kg/m2 at screening. BMI = body weight (kg) / (height(m))2

1. Subject has been receiving either of insulin therapy, sulfonylureas and insulin-stimulating agents at screening, or plans to receive any of these by the follow-up period of this study.
2. Subject plans to change the dietary therapy which has been taken until screening or to newly start the dietary therapy by the end of follow-up period of this study.
3. Subject has periodic exercise in the past six months before informed consent.
4. Subject applies to either of below at informed consent, screening or randomization;
- Type 1 diabetes mellitus
- complication of diabetic retinopathy except for simple retinopathy, other retinal neovascularization lesions or retinal complication treated by laser photocoagulation within six months
- complication of diabetic nephrology at Stage III or more
- complication of diabetic neuropathy
- complication of severe high blood pressure
- history or complication of severe cardiac disorder
- history or complication of cerebral vascular disorder
- history or complication of peripheral occlusive arterial disease
- complication of musculoskeletal disorders
- complication of respiratory disorders
- complication of acute or severe infectious disease
- complication of severe immune disorder which requires steroid or immunosuppressant therapy
- complication or history of malignancy.
5. Subject has either of below at screening or randomization
- Sitting systolic blood pressure >= 160 mmHg
- Sitting diastolic blood pressure >= 100 mmHg
- Sitting pulse rate >= 130 beats/min
- 12-lead electrocardiogram (12-ECG) >= Grade 2 defined in the classification criteria for severity of adverse drug reactions
6. Subject has either of below at screening;
- Brain natriuretic peptide (BNP) >= 100 pg/mL
- Fasting plasma glucose >= 250 mg/dL
- Positive urinary ketone bodies >= moderate level

Both

Type 2 diabetes mellitus

investigational material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

efficacy
Change from baseline in HbA1c
Up to Week 13

efficacy
Change from baseline in biochemistry values in plasma (fasting plasma glucose, glycoalbumin, fasting serum insulin, triglyceride, low density lipoprotein and high density lipoprotein cholesterol)
Up to Week 13
efficacy
Change from baseline in HOMA-R (fasting plasma glucose x fasting serum insulin / 405)
Up to Week 13
efficacy
Change from baseline in HOMA-beta (fasting serum insulin x 360 / (fasting plasma glucose - 63))
Up to Week 13
efficacy
Change from baseline in muscle mass
Up to Week 12
efficacy
Change from baseline in body fat percentage
Up to Week 12
efficacy
Change from baseline in waist circumference
Up to Week 13
efficacy
Change from baseline in body weight
Up to Week 13
efficacy
Change from baseline in SF-36 (Medical Outcomes Trust Short-Form 36-item v2)
Up to Week 13
efficacy
Change from baseline in blood pressure
Up to Week 13
safety
Safety assessed by incidence of adverse events
Up to Week 15

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June. 28, 2018