START-J: SiTAgliptin in eldeRly Trial in Japan

• Sponsor: Japan Association for Diabetes Education and Care (Other)
• Overall Status: Completed
• CT.gov ID: NCT01183104
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 305
• Location: 1
• Arms: 2
• Duration (Months): 53
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and the safety of sitagliptin and glimepiride in drug naïve elderly patients with Type 2 diabetes as evaluated by HbA1c change from baseline at 52 W as efficacy and incidence of hypoglycemia from randomization to 52 W as safety. The clinical hypotheses are non-inferiority of sitagliptin to glimepiride in efficacy as judged by HbA1c change from baseline at 52 W and superiority of sitagliptin to glimepiride in safety as judged by incidence of hypoglycemia in drug naïve elderly patients with T2DM. In addition, comparison of efficacy is extended to 104 W.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Sitagliptin; Drug: Glimepiride	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 305 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety Comparison of Sitagliptin and Glimepiride in Elderly Japanese Patients With Type 2 Diabetes
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sitagliptin	Drug: Sitagliptin; Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; estimate glomerular filtration rate (eGFR) 30=< <50).
Active Comparator: Glimepiride	Drug: Glimepiride; Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in HbA1c at 52 W [Baseline and 52 W]

2. Number of Participants With Hypoglycaemia [From baseline to 52 W]

Secondary Outcome Measures

1. The Number of Participants Achieving HbA1c < 6.9 % [52 W]

2. Change From Baseline in HOMA-β at 52 W [Baseline and 52 W]

   β cell function is measured by the Homeostatic Model Assessment(HOMA-β). HOMA β = [20 x fasting insulin (μU/mL)] / [fasting plasma glucose (mmol/L) - 3.5]

3. Change From Baseline in Insulin/Proinsulin Ratio at 52 W [Baseline and 52 W]

4. Change From Baseline in Body Weight at 52 W [Baseline and 52 W]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with type 2 diabetes who are oral hypoglycemic agent naive or, α-glucosidase inhibitor or biguanide monotherapy (to be washed out 4 weeks prior to randomization)

2. Signed informed consent obtained before any trial-related activities

3. Treatment with diet and exercise for 12 weeks and longer at screening

4. Age =>60 y.o.

5. Male and Female

6. HbA1c 6.9%=< <8.9%

Exclusion Criteria:

1. Active proliferative retinopathy or maculopathy requiring treatment

2. Liver dysfunction (>x2 of upper normal limit), moderate or severe renal dysfunction(serum Cr>1.5mg/dL in male, Cr>1.3mg/dL in female, eGFR<30), severe cardiac disease (NYHA III or IV), malignancy or uncontrolled hypertension (treated or untreated) as judged by the Investigator

3. Mental incapacity (including moderate or severe dementia) precluding adequate understanding and/or cooperation as judged by the Investigator

4. Recurrent hypoglycaemia or hypoglycaemic unawareness as judged by the investigator

5. Previous history of severe allergy to pharmaceutical products

6. Systemic glucocorticoids users or potential users

7. Suspected type 1 diabetes (including slowly progressive insulin dependent diabetes mellitus) or positive anti-glutamic acid decarboxylase antibody

8. Any condition that the investigator considers a potential obstacle to trial participation and/or data analysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Japan Association for Diabetes Education and Care	Chiyoda-Ku	Tokyo	Japan	102-0083

Sponsors and Collaborators

• Japan Association for Diabetes Education and Care
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Yasuo Terauchi, M.D., Ph.D., Yokohama City University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Japan Association for Diabetes Education and Care
• ClinicalTrials.gov Identifier: NCT01183104
• Other Study ID Numbers: START-J; UMIN000004047
• First Posted: Aug 17, 2010
• Last Update Posted: Apr 14, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Japan Association for Diabetes Education and Care: Type 2 Diabetes; Sitagliptin; Glimepiride; Elderly patients; Japanese
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Sitagliptin Phosphate; Glimepiride

Study Results

Participant Flow

Arm/Group Title	Sitagliptin	Glimepiride
Arm/Group Description	Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; estimate glomerular filtration rate (eGFR) 30=< <50).	Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg
Period Title: Overall Study
STARTED	153	152
Received Study Drug	148	143
Continued Treatment for 12 Weeks	143	129
Completed 52-week Treatment	119	111
Enrolled in Extension Study	80	61
COMPLETED	76	60
NOT COMPLETED	77	92

Baseline Characteristics

Arm/Group Title	Sitagliptin	Glimepiride	Total
Arm/Group Description	Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; eGFR 30=< <50).	Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg	Total of all reporting groups
Overall Participants	143	129	272
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.2 (5.4)	70.8 (5.5)	70.5 (5.5)
Sex: Female, Male (Count of Participants)
Female	69 48.3%	50 38.8%	119 43.8%
Male	74 51.7%	79 61.2%	153 56.3%
Region of Enrollment (participants) [Number]
Japan	143 100%	129 100%	272 100%
HbA1c (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	7.48 (0.68)	7.49 (0.67)	7.48 (0.67)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.1 (3.3)	24.2 (3.6)	24.2 (3.4)
eGFR (mL/min/1.73m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73m^2]	68.8 (17.1)	67.9 (17.1)	68.4 (17.1)
Body weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	60.9 (9.7)	60.9 (9.7)	60.9 (9.7)
HOMA-β (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	43.3 (33.7)	38.5 (34.0)	41.1 (33.9)
Insulin/Proinsulin Ratio (ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ratio]	0.217 (0.122)	0.205 (0.129)	0.211 (0.125)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c at 52 W
Time Frame	Baseline and 52 W

Outcome Measure Data

Analysis Population Description

Analysis set of evaluation for efficacy; Per Protocol Set.

Arm/Group Title	Sitagliptin	Glimepiride
Arm/Group Description	Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; eGFR 30=< <50).	Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg
Measure Participants	143	129
Least Squares Mean (95% Confidence Interval) [percent]	-0.66	-0.77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin, Glimepiride
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The pre-defined non-inferiority margin was 0.3%.
Statistical Test of Hypothesis	p-Value	0.087
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Participants With Hypoglycaemia
Time Frame	From baseline to 52 W

Outcome Measure Data

Analysis Population Description

Analysis set of evaluation for safety.

Arm/Group Title	Sitagliptin	Glimepiride
Arm/Group Description	Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; eGFR 30=< <50).	Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg
Measure Participants	148	143
Count of Participants [Participants]	7 4.9%	23 17.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin, Glimepiride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	The Number of Participants Achieving HbA1c < 6.9 %
Time Frame	52 W

Outcome Measure Data

Analysis Population Description

Analysis set of evaluation for efficacy; Per Protocol Set Some participants were not completed to 52 W.

Arm/Group Title	Sitagliptin	Glimepiride
Arm/Group Description	Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; eGFR 30=< <50).	Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg
Measure Participants	134	128
Count of Participants [Participants]	89 62.2%	86 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin, Glimepiride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Change From Baseline in HOMA-β at 52 W
Description	β cell function is measured by the Homeostatic Model Assessment(HOMA-β). HOMA β = [20 x fasting insulin (μU/mL)] / [fasting plasma glucose (mmol/L) - 3.5]
Time Frame	Baseline and 52 W

Outcome Measure Data

Analysis Population Description

Analysis set of evaluation for efficacy; Per Protocol Set. Some participants had loss of the measurement.

Arm/Group Title	Sitagliptin	Glimepiride
Arm/Group Description	Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; eGFR 30=< <50).	Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg
Measure Participants	122	119
Mean (Standard Deviation) [percent]	10.2 (35.7)	23.7 (56.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin, Glimepiride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Change From Baseline in Insulin/Proinsulin Ratio at 52 W
Time Frame	Baseline and 52 W

Outcome Measure Data

Analysis Population Description

Analysis set of evaluation for efficacy; Per Protocol Set. Some participants had loss of the measurement.

Arm/Group Title	Sitagliptin	Glimepiride
Arm/Group Description	Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; eGFR 30=< <50).	Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg
Measure Participants	120	112
Mean (Standard Deviation) [ratio]	-0.049 (0.111)	-0.002 (0.095)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin, Glimepiride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Change From Baseline in Body Weight at 52 W
Time Frame	Baseline and 52 W

Outcome Measure Data

Analysis Population Description

Analysis set of evaluation for efficacy; Per Protocol Set. Some participants had loss of the measurement.

Arm/Group Title	Sitagliptin	Glimepiride
Arm/Group Description	Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; eGFR 30=< <50).	Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg
Measure Participants	134	127
Mean (Standard Deviation) [kg]	-0.367 (2.441)	0.309 (2.915)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin, Glimepiride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Sitagliptin		Glimepiride
Arm/Group Description	Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; eGFR 30=< <50).		Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg
All Cause Mortality
	Sitagliptin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sitagliptin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/148 (8.8%)		3/143 (2.1%)
Blood and lymphatic system disorders
Hemorrhagic diathesis	1/148 (0.7%)		0/143 (0%)
Cardiac disorders
Acute myocardial infarction	1/148 (0.7%)		0/143 (0%)
Complete atrioventricular block	0/148 (0%)		1/143 (0.7%)
Takotsubo cardiomyopathy	1/148 (0.7%)		0/143 (0%)
Eye disorders
Hyphema	1/148 (0.7%)		0/143 (0%)
Gastrointestinal disorders
Colon polyp	0/148 (0%)		1/143 (0.7%)
General disorders
Death	0/148 (0%)		1/143 (0.7%)
Infections and infestations
Pneumonia	1/148 (0.7%)		0/143 (0%)
Infectious enteritis	1/148 (0.7%)		0/143 (0%)
Injury, poisoning and procedural complications
Globe rupture	1/148 (0.7%)		0/143 (0%)
Radius fracture	1/148 (0.7%)		0/143 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/148 (0.7%)		0/143 (0%)
Trismus	1/148 (0.7%)		0/143 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukemia	1/148 (0.7%)		0/143 (0%)
Tongue neoplasm malignant stage unspecified	1/148 (0.7%)		0/143 (0%)
Nervous system disorders
Cerebral infarction	1/148 (0.7%)		0/143 (0%)
Renal and urinary disorders
Renal failure	1/148 (0.7%)		0/143 (0%)
Skin and subcutaneous tissue disorders
Dermatitis exfoliative	1/148 (0.7%)		0/143 (0%)
Other (Not Including Serious) Adverse Events
	Sitagliptin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/148 (22.3%)		31/143 (21.7%)
Blood and lymphatic system disorders
Anemia	1/148 (0.7%)		0/143 (0%)
Mediastinal lymphadenopathy	1/148 (0.7%)		0/143 (0%)
Cardiac disorders
Atrial fibrillation	1/148 (0.7%)		0/143 (0%)
Heart failure	0/148 (0%)		1/143 (0.7%)
Myocardial ischemia	0/148 (0%)		1/143 (0.7%)
Ear and labyrinth disorders
Tinnitus	0/148 (0%)		1/143 (0.7%)
Eye disorders
Allergic conjunctivitis	0/148 (0%)		1/143 (0.7%)
Pterygium	0/148 (0%)		1/143 (0.7%)
Retinal hemorrhages	1/148 (0.7%)		0/143 (0%)
Vision blurred	0/148 (0%)		1/143 (0.7%)
Gastrointestinal disorders
Abdominal pain upper	0/148 (0%)		2/143 (1.4%)
Constipation	1/148 (0.7%)		1/143 (0.7%)
Diarrhea	1/148 (0.7%)		0/143 (0%)
Gastric ulcer	1/148 (0.7%)		0/143 (0%)
Erosive gastritis	0/148 (0%)		1/143 (0.7%)
Gastroesophageal reflux disease	1/148 (0.7%)		0/143 (0%)
Hemorrhoid	1/148 (0.7%)		0/143 (0%)
Stomatitis	1/148 (0.7%)		0/143 (0%)
General disorders
Face edema	0/148 (0%)		1/143 (0.7%)
Malaise	1/148 (0.7%)		1/143 (0.7%)
Fever	0/148 (0%)		1/143 (0.7%)
Hepatobiliary disorders
Choledocholith	1/148 (0.7%)		0/143 (0%)
Cholelithiasis	1/148 (0.7%)		0/143 (0%)
Liver Cyst	0/148 (0%)		1/143 (0.7%)
Hepatic function abnormal	0/148 (0%)		1/143 (0.7%)
Infections and infestations
Intestinal abscess	1/148 (0.7%)		0/143 (0%)
Appendicitis	1/148 (0.7%)		0/143 (0%)
Bronchitis	2/148 (1.4%)		0/143 (0%)
Cystitis	3/148 (2%)		0/143 (0%)
Herpes zoster	1/148 (0.7%)		0/143 (0%)
Nasopharyngitis	8/148 (5.4%)		7/143 (4.9%)
Pharyngitis	1/148 (0.7%)		0/143 (0%)
Helicobacter infection	0/148 (0%)		1/143 (0.7%)
Injury, poisoning and procedural complications
Injury	2/148 (1.4%)		0/143 (0%)
Sprained ligament	1/148 (0.7%)		0/143 (0%)
Wrist join fraction	1/148 (0.7%)		0/143 (0%)
Investigations
Blood pressure increased	0/148 (0%)		1/143 (0.7%)
Blood uric acid increased	1/148 (0.7%)		0/143 (0%)
Platelet count decreased	1/148 (0.7%)		0/143 (0%)
T-wave abnormality	0/148 (0%)		1/143 (0.7%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/148 (0%)		1/143 (0.7%)
Hyperuricemia	1/148 (0.7%)		0/143 (0%)
Hypoglycemia	0/148 (0%)		2/143 (1.4%)
Loss of appetite	1/148 (0.7%)		0/143 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/148 (0.7%)		0/143 (0%)
Osteoporosis	1/148 (0.7%)		0/143 (0%)
Spinal stenosis	0/148 (0%)		1/143 (0.7%)
Spondylosis deformans	1/148 (0.7%)		0/143 (0%)
Hygroma	0/148 (0%)		1/143 (0.7%)
Tenovaginitis	0/148 (0%)		1/143 (0.7%)
Disc protrusion	1/148 (0.7%)		0/143 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile ｄuct ｃancer	1/148 (0.7%)		0/143 (0%)
Colon ｃancer	2/148 (1.4%)		0/143 (0%)
Polycythemia vera	2/148 (1.4%)		0/143 (0%)
Thyroid neoplasm	1/148 (0.7%)		0/143 (0%)
Nervous system disorders
Cerebral infarction	0/148 (0%)		1/143 (0.7%)
Dizziness	0/148 (0%)		1/143 (0.7%)
Hypoesthesia	0/148 (0%)		2/143 (1.4%)
Loss of consciousness	0/148 (0%)		1/143 (0.7%)
Sciatica	1/148 (0.7%)		0/143 (0%)
Psychiatric disorders
Depression	1/148 (0.7%)		0/143 (0%)
Insomnia	0/148 (0%)		1/143 (0.7%)
Renal and urinary disorders
Ureteral calculus	0/148 (0%)		1/143 (0.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/148 (0.7%)		0/143 (0%)
Allergic rhinitis	0/148 (0%)		1/143 (0.7%)
Upper respiratory tract inflammation	3/148 (2%)		1/143 (0.7%)
Skin and subcutaneous tissue disorders
Eczema	0/148 (0%)		1/143 (0.7%)
Pruritus	1/148 (0.7%)		1/143 (0.7%)
Seborrheic dermatitis	0/148 (0%)		1/143 (0.7%)
Hives	0/148 (0%)		1/143 (0.7%)
Surgical and medical procedures
Ureteral stone removal	0/148 (0%)		1/143 (0.7%)
Dental care	1/148 (0.7%)		0/143 (0%)
Cataract operation	1/148 (0.7%)		0/143 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.