ORIENT: Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial

Sponsor

Daiichi Sankyo Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT00141453

Collaborator

(none)

577

Enrollment

Locations

Arms

69.1

Duration (Months)

288.5

Patients Per Site

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the effectiveness and safety of olmesartan versus placebo on the progression of diabetic renal disease.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Nephropathy Type 2 Diabetes Mellitus Proteinuria	Drug: olmesartan medoxomil Drug: Placebo Tablets	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

577 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

CS-866DM Phase 3 Clinical Study: A Double-Blind Controlled Trial in Patients With Diabetic Nephropathy and Overt Proteinuria Secondary to Type 2 Diabetes Mellitus

Study Start Date :

Apr 1, 2003

Actual Primary Completion Date :

Aug 1, 2008

Actual Study Completion Date :

Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Olmesartan medoxomil tablets 10mg to 40 mg	Drug: olmesartan medoxomil Tablets 10, 20, or 40 mg
Placebo Comparator: 2 Matching placebo tablets	Drug: Placebo Tablets Matching placebo tablets

Arm

Intervention/Treatment

Experimental: 1

Olmesartan medoxomil tablets 10mg to 40 mg

Drug: olmesartan medoxomil

Tablets 10, 20, or 40 mg

Placebo Comparator: 2

Matching placebo tablets

Drug: Placebo Tablets

Matching placebo tablets

Outcome Measures

Primary Outcome Measures

Renal Composite Outcomes [Randomization to 5 years]
first occurrence of any of the following events: Doubling of serum creatinine level; Death; End stage renal disease

Secondary Outcome Measures

Number of Participants Experiencing Cardiovascular Composite Outcomes [Within 5 years]
Number of participants experiencing the first occurence of any of the following: Cardiovascular death; non-fatal stroke; non-fatal myocardial infarction; hospitalization for unstable angina; lower extremity amputation; coronary/carotid/peripheral revascularization.
The Change in Proteinuria [Randomization to 5 years]
The median percentage change from baseline value in urinary protein:creatinine ratio
Reciprocal (1/Serum Creatinine) of Serum Creatinine [Randomization to 5 years]
The amount of serum creatinine was determined by blood tests periodically during the study. The amount of creatinine is an indication of kidney function. The reciprocal of serum creatinine is used in an equation to determine the change in kidney function from baseline. The reciprocal of the serum creatinine was monitored to detect kidney function changes over duration of the study.

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

clinical diagnosis of diabetic nephropathy in patients with type 2 diabetes
albumin-to-creatinine ratio >= 300 mg/g creatinine in first morning urinalysis
serum creatinine between 1.0 and 2.5 mg/dL in women and between 1.2 and 2.5 mg/dL in men

Exclusion Criteria:

type 1 diabetes
non-diabetic nephropathy
history of myocardial infarction
history of cardiac bypass grafting within 3 months
history of percutaneous coronary intervention (PCI) within 6 months
history of carotid artery or peripheral artery revascularization within 6 months
stroke or transient ischemic attack (TIA) within 1 year
unstable angina pectoris
heart failure of NYHA functional classes III or IV
rapid progression of kidney disease within 3 months
severe orthostatic hypotension
serum potassium level =<3.5 mEq(mmol)/L or =>5.5 mEq(mmol)L
history of rapid elevation of the serum creatinine level after starting treatment with AII receptor antagonists or ACE inhibitors
poor glycemic control: HbA1c level =>11%
history of myocardial infarction (MI) or coronary artery bypass grafting (CABG) within 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Hong Kong		China
2		Tokyo		Japan

Sponsors and Collaborators

Daiichi Sankyo Co., Ltd.

Investigators

Study Director: Study Manager, R&D Division, Daiichi Sankyo Co., Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00141453

Other Study ID Numbers:

ORIENT

First Posted:

Sep 1, 2005

Last Update Posted:

May 10, 2011

Last Verified:

May 1, 2011

Keywords provided by , ,

angiotensin II type I receptor blockers

diabetic nephropathy

end-stage renal disease

renal failure

type 2 diabetes

olmesartan medoxomil

Additional relevant MeSH terms:

Kidney Diseases

Diabetic Nephropathies

Proteinuria

Diabetes Mellitus

Diabetes Mellitus, Type 2

Olmesartan

Olmesartan Medoxomil

Study Results

Participant Flow

Recruitment Details	The study population was defined by the inclusion criteria. This study was carried out at 74 centers in Japan and 3 centers in Hong Kong. After the screening visit, the patients that met inclusion and exclusion criteria were selected to participate in the study. First Patient in: 19 May 2003.
Pre-assignment Detail	During 6-week screening, patients were treated with placebo and assessed for eligibility. Eligible patients were assigned to 10mg of olmesartan or placebo. 857 were screened; 577 were randomized; 566=the full analysis set (11 who completed were excluded for protocol violations). Data are based on the participants in the full analysis set.

Arm/Group Title	Olmesartan Medoxomil	Placebo Comparator
Arm/Group Description	Experimental: Olmesartan medoxomil tablets 10mg to 40 mg	Matching placebo tablets
Period Title: Overall Study
STARTED	288	289
COMPLETED	282	284
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Olmesartan Medoxomil	Placebo Comparator	Total
Arm/Group Description	Experimental: Olmesartan medoxomil tablets 10mg to 40 mg	Matching placebo tablets	Total of all reporting groups
Overall Participants	282	284	566
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (8.1)	59.2 (8.1)	59.2 (8.1)
Sex: Female, Male (Count of Participants)
Female	83 29.4%	92 32.4%	175 30.9%
Male	199 70.6%	192 67.6%	391 69.1%
Region of Enrollment (participants) [Number]
East Asia	282 100%	284 100%	566 100%
Use of ACE inhibitors (participants) [Number]
Used ACE Inhibitors	205 72.7%	209 73.6%	414 73.1%
Did not use ACE Inhibitors	77 27.3%	75 26.4%	152 26.9%
Diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	77.8 (10.4)	77.2 (10.6)	77.5 (10.5)
HbA1c (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	7.11 (1.20)	7.05 (1.24)	7.08 (1.22)
Serum creatinine (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.62 (0.32)	1.62 (0.35)	1.62 (0.34)
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	141.7 (17.0)	140.8 (18.0)	141.3 (17.5)
Urinary albumin:creatinine ratio (g/g) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [g/g]	1.70	1.69	1.69
Urinary protein: creatinine ratio (g/g) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [g/g]	2.19	2.05	2.12

Outcome Measures

1. Primary Outcome

Title	Renal Composite Outcomes
Description	first occurrence of any of the following events: Doubling of serum creatinine level; Death; End stage renal disease
Time Frame	Randomization to 5 years

Outcome Measure Data

Analysis Population Description
Full analysis set=566

Arm/Group Title	Olmesartan Medoxomil	Placebo Comparator
Arm/Group Description	Experimental: Olmesartan medoxomil tablets 10mg to 40 mg	Matching placebo tablets
Measure Participants	282	284
Number [participants]	116 41.1%	129 45.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan Medoxomil, Placebo Comparator
	Comments	We planned to collect 400 patients to detect 35% risk reduction for renal outcome in olmesartan group with 80% power at 2-sided .05 alpha level. The Cox regression model was applied to estimate the hazard ratios (HR)between treatment groups with 95% confidence intervals for the renal and cardiovascular composite event rate.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Regression, Cox
	Comments	The covariates were urinary albumin:creatinine ratio and serum creatinine at baseline & regions (Japan/Hong Kong) for the renal composite event rate.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	() 95% 0.75 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants Experiencing Cardiovascular Composite Outcomes
Description	Number of participants experiencing the first occurence of any of the following: Cardiovascular death; non-fatal stroke; non-fatal myocardial infarction; hospitalization for unstable angina; lower extremity amputation; coronary/carotid/peripheral revascularization.
Time Frame	Within 5 years

Outcome Measure Data

Analysis Population Description
Full analysis set=566

Arm/Group Title	Olmesartan Medoxomil	Placebo Comparator
Arm/Group Description	Experimental: Olmesartan medoxomil tablets 10mg to 40 mg	Matching placebo tablets
Measure Participants	282	284
Number [participants]	40 14.2%	53 18.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan Medoxomil, Placebo Comparator
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.039
	Comments
	Method	Regression, Cox
	Comments	Covariates baseline urinary albumin:creatinine ratio, age and history of cardiovascular disease for cardiovascular composite event rate.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	() 95% 0.43 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	The Change in Proteinuria
Description	The median percentage change from baseline value in urinary protein:creatinine ratio
Time Frame	Randomization to 5 years

Outcome Measure Data

Analysis Population Description
Full analysis set=566

Arm/Group Title	Olmesartan Medoxomil	Placebo Comparator
Arm/Group Description	Experimental: Olmesartan medoxomil tablets 10mg to 40 mg	Matching placebo tablets
Measure Participants	282	284
12-week value	-19.5	12.6
48-week value	-20.0	6.9
144 -week value	-24.9	3.1

4. Secondary Outcome

Title	Reciprocal (1/Serum Creatinine) of Serum Creatinine
Description	The amount of serum creatinine was determined by blood tests periodically during the study. The amount of creatinine is an indication of kidney function. The reciprocal of serum creatinine is used in an equation to determine the change in kidney function from baseline. The reciprocal of the serum creatinine was monitored to detect kidney function changes over duration of the study.
Time Frame	Randomization to 5 years

Outcome Measure Data

Analysis Population Description
Full analysis set=566

Arm/Group Title	Olmesartan Medoxomil	Placebo Comparator
Arm/Group Description	Experimental: Olmesartan medoxomil tablets 10mg to 40 mg	Matching placebo tablets
Measure Participants	282	284
Median (Inter-Quartile Range) [dL/mg/year]	-0.071	-0.089

Adverse Events

	Olmesartan Medoxomil		Placebo Comparator
Time Frame	From baseline to up to 226 weeks
Adverse Event Reporting Description

Arm/Group Title	Olmesartan Medoxomil		Placebo Comparator
Arm/Group Description	Experimental: Olmesartan medoxomil tablets 10mg to 40 mg		Matching placebo tablets
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Olmesartan Medoxomil		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	147/287 (51.2%)		171/288 (59.4%)
Blood and lymphatic system disorders
Anaemia	1/287 (0.3%)		6/288 (2.1%)
Iron deficiency anaemia	0/287 (0%)		4/288 (1.4%)
Lymphadenitis	1/287 (0.3%)		0/288 (0%)
Neprogenic anaemia	0/287 (0%)		1/288 (0.3%)
Cardiac disorders
Acute myocardial infarction	25/287 (8.7%)		35/288 (12.2%)
Angina pectoris	2/287 (0.7%)		2/288 (0.7%)
Angina unstable	2/287 (0.7%)		2/288 (0.7%)
Aortic valve stenosis	0/287 (0%)		1/288 (0.3%)
Atrial fibrillation	1/287 (0.3%)		2/288 (0.7%)
Antrioventricular block complete	0/287 (0%)		1/288 (0.3%)
Atrioventricular block second degree	0/287 (0%)		1/288 (0.3%)
Bradycardia	0/287 (0%)		1/288 (0.3%)
Cardiac failure	3/287 (1%)		6/288 (2.1%)
Cardiac failure acute	2/287 (0.7%)		7/288 (2.4%)
Cardiac failure chronic	1/287 (0.3%)		0/288 (0%)
Cardiac failure congestive	12/287 (4.2%)		12/288 (4.2%)
Coronary artery disease	1/287 (0.3%)		0/288 (0%)
Myocardial infarction	0/287 (0%)		1/288 (0.3%)
Myocardial ischaemia	1/287 (0.3%)		2/288 (0.7%)
Nodal arrhythmia	1/287 (0.3%)		0/288 (0%)
Palpitations	0/287 (0%)		1/288 (0.3%)
sick sinus syndrome	1/287 (0.3%)		1/288 (0.3%)
supraventricular tachycardia	0/287 (0%)		1/288 (0.3%)
tachycardia paroxysmal	0/287 (0%)		1/288 (0.3%)
Ischaemic cardiomyopathy	0/287 (0%)		1/288 (0.3%)
silent myocardial infarction	0/287 (0%)		1/288 (0.3%)
Acute coronary syndrome	3/287 (1%)		4/288 (1.4%)
Ear and labyrinth disorders
Deafness neurosensory	1/287 (0.3%)		0/288 (0%)
Vertigo	2/287 (0.7%)		1/288 (0.3%)
vertigo positional	0/287 (0%)		1/288 (0.3%)
sudden hearing loss	1/287 (0.3%)		0/288 (0%)
Eye disorders
angle closure glaucoma	1/287 (0.3%)		0/288 (0%)
aphakia	1/287 (0.3%)		0/288 (0%)
boardline glaucoma	1/287 (0.3%)		0/288 (0%)
Cataract	12/287 (4.2%)		11/288 (3.8%)
Cataract diabetic	0/287 (0%)		1/288 (0.3%)
Diabetic retinal oedema	1/287 (0.3%)		0/288 (0%)
Glaucoma	2/287 (0.7%)		0/288 (0%)
macular oedema	1/287 (0.3%)		1/288 (0.3%)
maculopathy	0/287 (0%)		1/288 (0.3%)
retinal detachment	2/287 (0.7%)		3/288 (1%)
retinal hemorrhage	0/287 (0%)		1/288 (0.3%)
retinal tear	0/287 (0%)		1/288 (0.3%)
retinopathy proliferative	1/287 (0.3%)		0/288 (0%)
vitreous haemorrhage	7/287 (2.4%)		8/288 (2.8%)
macular hole	0/287 (0%)		1/288 (0.3%)
Gastrointestinal disorders
Adominal distension	0/287 (0%)		1/288 (0.3%)
abdominal pain	1/287 (0.3%)		0/288 (0%)
abdominal pain lower	0/287 (0%)		1/288 (0.3%)
anal fistula	1/287 (0.3%)		0/288 (0%)
appendicitis perforated	1/287 (0.3%)		0/288 (0%)
ascites	1/287 (0.3%)		1/288 (0.3%)
colitis	1/287 (0.3%)		0/288 (0%)
colonic polyp	5/287 (1.7%)		11/288 (3.8%)
constipation	0/287 (0%)		1/288 (0.3%)
diarroea	0/287 (0%)		3/288 (1%)
duodenal polyp	1/287 (0.3%)		0/288 (0%)
duodenal ulcer	1/287 (0.3%)		0/288 (0%)
duodenal ulcer haemorrhage	1/287 (0.3%)		0/288 (0%)
entrocolitis	1/287 (0.3%)		0/288 (0%)
gastric ulcer	1/287 (0.3%)		1/288 (0.3%)
gastric ulcer haemorrhage	2/287 (0.7%)		0/288 (0%)
gastritis	2/287 (0.7%)		2/288 (0.7%)
gastritis erosive	0/287 (0%)		1/288 (0.3%)
gastritis haemorrhagic	0/287 (0%)		1/288 (0.3%)
haemorrhoids	1/287 (0.3%)		1/288 (0.3%)
inguinal hernia	0/287 (0%)		1/288 (0.3%)
intestinal obstruction	1/287 (0.3%)		2/288 (0.7%)
Mallory-Weiss syndrome	1/287 (0.3%)		2/288 (0.7%)
Melaena	1/287 (0.3%)		0/288 (0%)
Nausea	0/287 (0%)		1/288 (0.3%)
Oesophagitis	0/287 (0%)		2/288 (0.7%)
Pancreatitis acute	0/287 (0%)		1/288 (0.3%)
Peptic ulcer	0/287 (0%)		1/288 (0.3%)
Salivary gland calculus	0/287 (0%)		1/288 (0.3%)
Stomach discomfort	1/287 (0.3%)		0/288 (0%)
Umbilical hernia	1/287 (0.3%)		0/288 (0%)
Upper gastrointestinal haemorrhage	0/287 (0%)		1/288 (0.3%)
Varices oesophageal	0/287 (0%)		2/288 (0.7%)
General disorders
Chest discomfort	1/287 (0.3%)		0/288 (0%)
Chest pain	4/287 (1.4%)		1/288 (0.3%)
Chills	1/287 (0.3%)		0/288 (0%)
Generalised oedema	1/287 (0.3%)		3/288 (1%)
Hernia	0/287 (0%)		1/288 (0.3%)
Malaise	0/287 (0%)		1/288 (0.3%)
Oedema	2/287 (0.7%)		2/288 (0.7%)
Oedema peripheral	0/287 (0%)		3/288 (1%)
Sudden death	3/287 (1%)		3/288 (1%)
Hepatobiliary disorders
Bile duct stone	1/287 (0.3%)		1/288 (0.3%)
Cholecystitis chronic	0/287 (0%)		1/288 (0.3%)
Cholelithiasis	1/287 (0.3%)		0/288 (0%)
Cirrhosis alcoholic	0/287 (0%)		1/288 (0.3%)
Hepatic function abnormal	0/287 (0%)		2/288 (0.7%)
Hepatitis	0/287 (0%)		1/288 (0.3%)
Immune system disorders
Anaphylactic shock	1/287 (0.3%)		0/288 (0%)
Infections and infestations
Appendicitis	1/287 (0.3%)		2/288 (0.7%)
Arthritis viral	0/287 (0%)		1/288 (0.3%)
Bartholin's abscess	0/287 (0%)		1/288 (0.3%)
Bronchitis	0/287 (0%)		2/288 (0.7%)
Bronchopneumonia	0/287 (0%)		1/288 (0.3%)
Cellulitis	5/287 (1.7%)		4/288 (1.4%)
Diabetic gangrene	1/287 (0.3%)		0/288 (0%)
Gangrene	2/287 (0.7%)		0/288 (0%)
Gastroenteritis	7/287 (2.4%)		3/288 (1%)
Gastroenteritis viral	0/287 (0%)		1/288 (0.3%)
Hepatitis C	0/287 (0%)		1/288 (0.3%)
Herpes zoster	1/287 (0.3%)		1/288 (0.3%)
HIV infection	0/287 (0%)		1/288 (0.3%)
Infected sebaceous cyst	1/287 (0.3%)		0/288 (0%)
Influenza	1/287 (0.3%)		0/288 (0%)
Lobar pneumonia	1/287 (0.3%)		0/288 (0%)
Lower respiratory tract infection	5/287 (1.7%)		6/288 (2.1%)
Nasopharyngitis	1/287 (0.3%)		1/288 (0.3%)
Otitis media	0/287 (0%)		1/288 (0.3%)
Perianal abscess	0/287 (0%)		1/288 (0.3%)
Pneumonia	5/287 (1.7%)		8/288 (2.8%)
Postoperative wound infection	0/287 (0%)		1/288 (0.3%)
Pyothorax	0/287 (0%)		1/288 (0.3%)
Sepsis	0/287 (0%)		4/288 (1.4%)
Sialoadenitis	0/287 (0%)		1/288 (0.3%)
Subcutaneous abscess	1/287 (0.3%)		0/288 (0%)
Upper respiratory tract infection	0/287 (0%)		4/288 (1.4%)
Urinary tract infection	7/287 (2.4%)		6/288 (2.1%)
Urosepsis	0/287 (0%)		1/288 (0.3%)
Abscess limb	1/287 (0.3%)		1/288 (0.3%)
Enteritis infectious	2/287 (0.7%)		0/288 (0%)
Injury, poisoning and procedural complications
Facial bones fracture	1/287 (0.3%)		0/288 (0%)
Femur fracture	1/287 (0.3%)		0/288 (0%)
Fracture	1/287 (0.3%)		1/288 (0.3%)
Humerus fracture	0/287 (0%)		1/288 (0.3%)
Overdose	1/287 (0.3%)		1/288 (0.3%)
Patella fracture	0/287 (0%)		1/288 (0.3%)
Radius fracture	1/287 (0.3%)		0/288 (0%)
Skull fractured base	1/287 (0.3%)		0/288 (0%)
Spinal cord injury cervical	1/287 (0.3%)		0/288 (0%)
Subdural haematoma	0/287 (0%)		1/288 (0.3%)
Subdural haemorrhage	1/287 (0.3%)		0/288 (0%)
Traumatic fracture	0/287 (0%)		1/288 (0.3%)
Excoriation	0/287 (0%)		1/288 (0.3%)
Contusion	1/287 (0.3%)		0/288 (0%)
Intraocular lens dislocation	0/287 (0%)		1/288 (0.3%)
Brain contusion	0/287 (0%)		1/288 (0.3%)
Thermal burn	0/287 (0%)		1/288 (0.3%)
Eye injury	0/287 (0%)		1/288 (0.3%)
Neck injury	0/287 (0%)		1/288 (0.3%)
Medical device site reaction	0/287 (0%)		1/288 (0.3%)
Ligament rupture	0/287 (0%)		1/288 (0.3%)
Investigations
Alanine aminotransferase increased	1/287 (0.3%)		3/288 (1%)
Arteriogram coronary	1/287 (0.3%)		1/288 (0.3%)
Aspartate aminotransferase increased	1/287 (0.3%)		3/288 (1%)
Bilirubin conjugated increased	0/287 (0%)		1/288 (0.3%)
Blood bilirubin increased	1/287 (0.3%)		1/288 (0.3%)
Blood calcium decreased	0/287 (0%)		1/288 (0.3%)
Blood chloride decreased	0/287 (0%)		1/288 (0.3%)
Blood creatine phosphokinase increased	2/287 (0.7%)		5/288 (1.7%)
Blood creatinine increased	12/287 (4.2%)		15/288 (5.2%)
Blood glucose decreased	2/287 (0.7%)		5/288 (1.7%)
Blood glucose increased	2/287 (0.7%)		2/288 (0.7%)
Blood lactate dehydrogenase increased	0/287 (0%)		1/288 (0.3%)
Blood potassium decreased	1/287 (0.3%)		0/288 (0%)
Blood potassium increased	0/287 (0%)		2/288 (0.7%)
Blood pressure increased	1/287 (0.3%)		0/288 (0%)
Blood urea increased	6/287 (2.1%)		7/288 (2.4%)
C-reactive protein increased	3/287 (1%)		3/288 (1%)
Colonoscopy	0/287 (0%)		2/288 (0.7%)
Gamma-glutamyltransferase increased	1/287 (0.3%)		2/288 (0.7%)
Glycosylated haemoglobin increased	1/287 (0.3%)		1/288 (0.3%)
Haematocrit decreased	2/287 (0.7%)		4/288 (1.4%)
Haemoglobin decreased	3/287 (1%)		5/288 (1.7%)
International normalised ratio increased	0/287 (0%)		1/288 (0.3%)
Myoglobin blood increased	0/287 (0%)		1/288 (0.3%)
Neutrophil count increased	0/287 (0%)		1/288 (0.3%)
Nuclear magnetic resonance imaging brain abnormal	1/287 (0.3%)		0/288 (0%)
Red blood cell count decreased	2/287 (0.7%)		4/288 (1.4%)
Serum ferritin decreased	0/287 (0%)		1/288 (0.3%)
Weight increased	2/287 (0.7%)		1/288 (0.3%)
White blood cell count increased	3/287 (1%)		2/288 (0.7%)
Blood phosphorus increased	0/287 (0%)		3/288 (1%)
Creatinine urine increased	1/287 (0.3%)		0/288 (0%)
Sleep study	5/287 (1.7%)		1/288 (0.3%)
Brain natriuretic peptide increased	0/287 (0%)		1/288 (0.3%)
Urine protein/creatinine ratio decreased	1/287 (0.3%)		0/288 (0%)
Urine protein/creatinine ratio increased	0/287 (0%)		1/288 (0.3%)
Cardiac function test	0/287 (0%)		1/288 (0.3%)
Blood alkaline phosphatase increased	1/287 (0.3%)		3/288 (1%)
Dexamethasone suppression test positive	0/287 (0%)		2/288 (0.7%)
Dexamethasone suppression test	1/287 (0.3%)		1/288 (0.3%)
Renal function test	1/287 (0.3%)		0/288 (0%)
Pulmonary function test abnormal	1/287 (0.3%)		0/288 (0%)
Endoscopy large bowel	1/287 (0.3%)		0/288 (0%)
Investigation	1/287 (0.3%)		1/288 (0.3%)
Nephrological examination	1/287 (0.3%)		0/288 (0%)
Metabolism and nutrition disorders
Anorexia	0/287 (0%)		1/288 (0.3%)
Dehydration	1/287 (0.3%)		2/288 (0.7%)
Diabetes mellitus inadequate control	7/287 (2.4%)		8/288 (2.8%)
Diabetic ketoacidosis	0/287 (0%)		1/288 (0.3%)
Fluid overload	5/287 (1.7%)		10/288 (3.5%)
Fluid retention	3/287 (1%)		1/288 (0.3%)
Gout	1/287 (0.3%)		1/288 (0.3%)
Hyperglycaemia	4/287 (1.4%)		4/288 (1.4%)
Hyperkalaemia	10/287 (3.5%)		6/288 (2.1%)
Hypocalcaemia	0/287 (0%)		1/288 (0.3%)
Hypoglycaemia	8/287 (2.8%)		15/288 (5.2%)
Hypoglycaemia unawareness	1/287 (0.3%)		0/288 (0%)
Hypokalaemia	1/287 (0.3%)		0/288 (0%)
Hyponatraemia	1/287 (0.3%)		1/288 (0.3%)
Metabolic acidosis	0/287 (0%)		2/288 (0.7%)
Diabetic foot	0/287 (0%)		1/288 (0.3%)
Decreased appetite	0/287 (0%)		1/288 (0.3%)
Musculoskeletal and connective tissue disorders
Amyotrophy	1/287 (0.3%)		0/288 (0%)
Back pain	1/287 (0.3%)		1/288 (0.3%)
Gouty arthritis	2/287 (0.7%)		1/288 (0.3%)
Joint contracture	1/287 (0.3%)		0/288 (0%)
Lumbar spinal stenosis	1/287 (0.3%)		1/288 (0.3%)
Myositis	1/287 (0.3%)		1/288 (0.3%)
Neuropathic arthropathy	1/287 (0.3%)		0/288 (0%)
Periarthritis	0/287 (0%)		1/288 (0.3%)
Rhabdomyolysis	0/287 (0%)		2/288 (0.7%)
Spinal osteoarthritis	2/287 (0.7%)		0/288 (0%)
Synovitis	0/287 (0%)		1/288 (0.3%)
Tenosynovitis	1/287 (0.3%)		0/288 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/287 (0%)		1/288 (0.3%)
Carcinoid tumour of the gastrointestinal tract	1/287 (0.3%)		0/288 (0%)
Colon cancer	0/287 (0%)		2/288 (0.7%)
Gastric cancer	1/287 (0.3%)		2/288 (0.7%)
Hepatic neoplasm	0/287 (0%)		1/288 (0.3%)
Hepatic neoplasm malignant	0/287 (0%)		1/288 (0.3%)
Metastases to liver	0/287 (0%)		1/288 (0.3%)
Non-Hodgkin's lymphoma	1/287 (0.3%)		0/288 (0%)
Small cell lung cancer stage unspecified	0/287 (0%)		1/288 (0.3%)
Lung neoplasm malignant	0/287 (0%)		1/288 (0.3%)
Large intestine carcinoma	1/287 (0.3%)		2/288 (0.7%)
Prostate cancer	0/287 (0%)		1/288 (0.3%)
Pituitary tumour benign	0/287 (0%)		1/288 (0.3%)
Non-small cell lung cancer	1/287 (0.3%)		0/288 (0%)
Lung neoplasm	0/287 (0%)		1/288 (0.3%)
Nervous system disorders
Altered state of consciousness	0/287 (0%)		1/288 (0.3%)
Cerebellar infarction	2/287 (0.7%)		2/288 (0.7%)
Cerebrovascular accident	1/287 (0.3%)		1/288 (0.3%)
Convulsion	0/287 (0%)		1/288 (0.3%)
Diabetic autonomic neuropathy	1/287 (0.3%)		0/288 (0%)
Dizziness	3/287 (1%)		1/288 (0.3%)
Dizziness postural	0/287 (0%)		1/288 (0.3%)
Epilepsy	1/287 (0.3%)		0/288 (0%)
Intracranial aneurysm	0/287 (0%)		1/288 (0.3%)
Loss of consciousness	2/287 (0.7%)		0/288 (0%)
Thrombotic cerebral infarction	0/287 (0%)		1/288 (0.3%)
Syncope	0/287 (0%)		3/288 (1%)
Mononeuropathy multiplex	0/287 (0%)		1/288 (0.3%)
Syncope vasovagal	1/287 (0.3%)		0/288 (0%)
Vertebrobasilar insufficiency	1/287 (0.3%)		0/288 (0%)
VIth nerve paralysis	1/287 (0.3%)		0/288 (0%)
Cubital tunnel syndrome	0/287 (0%)		1/288 (0.3%)
Cranial nerve paralysis	0/287 (0%)		1/288 (0.3%)
Psychiatric disorders
Completed suicide	1/287 (0.3%)		1/288 (0.3%)
Confusional state	0/287 (0%)		1/288 (0.3%)
Depression	1/287 (0.3%)		0/288 (0%)
Dysthymic disorder	0/287 (0%)		1/288 (0.3%)
Psychosomatic disease	1/287 (0.3%)		0/288 (0%)
Renal and urinary disorders
Azotaemia	1/287 (0.3%)		1/288 (0.3%)
Nephropathy toxic	1/287 (0.3%)		0/288 (0%)
Nephrotic syndrome	1/287 (0.3%)		0/288 (0%)
Neurogenic bladder	0/287 (0%)		1/288 (0.3%)
Renal failure	1/287 (0.3%)		0/288 (0%)
Renal failure acute	7/287 (2.4%)		3/288 (1%)
Renal failure chronic	4/287 (1.4%)		2/288 (0.7%)
Urinary retention	0/287 (0%)		1/288 (0.3%)
Diabetic nephropathy	2/287 (0.7%)		2/288 (0.7%)
Renal impairment	4/287 (1.4%)		2/288 (0.7%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/287 (0.7%)		0/288 (0%)
Epididymitis	1/287 (0.3%)		1/288 (0.3%)
Prostatomegaly	2/287 (0.7%)		0/288 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/287 (0%)		1/288 (0.3%)
Asthma	1/287 (0.3%)		0/288 (0%)
Asthma late onset	0/287 (0%)		1/288 (0.3%)
Chronic obstructive pulmonary disease	1/287 (0.3%)		0/288 (0%)
Dyspnoea	1/287 (0.3%)		0/288 (0%)
Epistaxis	0/287 (0%)		1/288 (0.3%)
Haemoptysis	1/287 (0.3%)		1/288 (0.3%)
Haemothorax	0/287 (0%)		1/288 (0.3%)
Laryngeal oedema	0/287 (0%)		1/288 (0.3%)
Pleural effusion	3/287 (1%)		1/288 (0.3%)
Pleural fibrosis	0/287 (0%)		1/288 (0.3%)
Pleurisy	0/287 (0%)		1/288 (0.3%)
Pneumonia aspiration	0/287 (0%)		1/288 (0.3%)
Pulmonary congestion	1/287 (0.3%)		0/288 (0%)
Pulmonary oedema	2/287 (0.7%)		0/288 (0%)
Sleep apnoea syndrome	3/287 (1%)		1/288 (0.3%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/287 (0%)		1/288 (0.3%)
Dermatitis	0/287 (0%)		1/288 (0.3%)
Eczema	0/287 (0%)		1/288 (0.3%)
Skin ulcer	2/287 (0.7%)		0/288 (0%)
Urticaria	1/287 (0.3%)		0/288 (0%)
Surgical and medical procedures
Catheterisation cardiac	1/287 (0.3%)		4/288 (1.4%)
Uterine prolapse repair	1/287 (0.3%)		0/288 (0%)
Vitrectomy	1/287 (0.3%)		0/288 (0%)
Glaucoma surgery	1/287 (0.3%)		0/288 (0%)
Coronary angioplasty	2/287 (0.7%)		2/288 (0.7%)
Continuous positive airway pressure	1/287 (0.3%)		1/288 (0.3%)
Hospitalisation	3/287 (1%)		3/288 (1%)
Surgical vascular shunt	0/287 (0%)		1/288 (0.3%)
Elective surgery	0/287 (0%)		1/288 (0.3%)
Arteriovenous shunt operation	2/287 (0.7%)		2/288 (0.7%)
Tooth extraction	1/287 (0.3%)		0/288 (0%)
Cataract operation	9/287 (3.1%)		13/288 (4.5%)
Blood pressure management	1/287 (0.3%)		0/288 (0%)
Percutaneous coronary intervention	0/287 (0%)		1/288 (0.3%)
Vascular disorders
Aortic aneurysm	0/287 (0%)		1/288 (0.3%)
Arteriosclerosis	1/287 (0.3%)		0/288 (0%)
Hypertension	0/287 (0%)		1/288 (0.3%)
Hypotension	4/287 (1.4%)		1/288 (0.3%)
Orthostatic hypotension	0/287 (0%)		2/288 (0.7%)
Peripheral vascular disorder	0/287 (0%)		1/288 (0.3%)
Deep vein thrombosis	1/287 (0.3%)		0/288 (0%)
Blood pressure inadequately controlled	2/287 (0.7%)		0/288 (0%)
Arteriosclerosis obliterans	0/287 (0%)		1/288 (0.3%)
Other (Not Including Serious) Adverse Events
	Olmesartan Medoxomil		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	264/287 (92%)		265/288 (92%)
Eye disorders
Cataract	44/287 (15.3%)		45/288 (15.6%)
Diabetic retinopathy	26/287 (9.1%)		24/288 (8.3%)
Vitreous haemorrhage	12/287 (4.2%)		16/288 (5.6%)
Gastrointestinal disorders
Colonic polyp	9/287 (3.1%)		17/288 (5.9%)
Constipation	49/287 (17.1%)		41/288 (14.2%)
Diarrhoea	28/287 (9.8%)		40/288 (13.9%)
Gastritis	16/287 (5.6%)		19/288 (6.6%)
Nausea	15/287 (5.2%)		12/288 (4.2%)
Toothache	16/287 (5.6%)		16/288 (5.6%)
General disorders
Chest discomfort	16/287 (5.6%)		18/288 (6.3%)
Chest pain	19/287 (6.6%)		9/288 (3.1%)
Malaise	7/287 (2.4%)		16/288 (5.6%)
Oedema	17/287 (5.9%)		20/288 (6.9%)
Oedema peripheral	65/287 (22.6%)		76/288 (26.4%)
Infections and infestations
Bronchitis	21/287 (7.3%)		22/288 (7.6%)
Gastroenteritis	26/287 (9.1%)		14/288 (4.9%)
Infuenza	15/287 (5.2%)		11/288 (3.8%)
Nasopharyngitis	105/287 (36.6%)		106/288 (36.8%)
Upper respiratory tract infection	59/287 (20.6%)		57/288 (19.8%)
Urinary tract infection	19/287 (6.6%)		17/288 (5.9%)
Injury, poisoning and procedural complications
Contusion	25/287 (8.7%)		16/288 (5.6%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	13/287 (4.5%)		15/288 (5.2%)
Gout	18/287 (6.3%)		16/288 (5.6%)
Hyperkalaemia	68/287 (23.7%)		61/288 (21.2%)
Hypoglycaemia	69/287 (24%)		69/288 (24%)
Musculoskeletal and connective tissue disorders
Arthralgia	40/287 (13.9%)		33/288 (11.5%)
Back pain	47/287 (16.4%)		42/288 (14.6%)
Muscle spasms	21/287 (7.3%)		37/288 (12.8%)
Musculoskeletal pain	19/287 (6.6%)		22/288 (7.6%)
Pain in extremity	28/287 (9.8%)		34/288 (11.8%)
Spinal osteoarthritis	19/287 (6.6%)		17/288 (5.9%)
Nervous system disorders
Dizziness	41/287 (14.3%)		50/288 (17.4%)
Dizziness postural	14/287 (4.9%)		17/288 (5.9%)
Headache	26/287 (9.1%)		24/288 (8.3%)
Hypoaesthesia	18/287 (6.3%)		19/288 (6.6%)
Psychiatric disorders
Insomnia	20/287 (7%)		17/288 (5.9%)
Respiratory, thoracic and mediastinal disorders
Cough	60/287 (20.9%)		57/288 (19.8%)
Epistaxis	9/287 (3.1%)		17/288 (5.9%)
Rhinorrhoea	15/287 (5.2%)		15/288 (5.2%)
Upper respiratory tract inflammation	37/287 (12.9%)		23/288 (8%)
Skin and subcutaneous tissue disorders
Eczema	27/287 (9.4%)		27/288 (9.4%)
Pruritus	21/287 (7.3%)		25/288 (8.7%)
Vascular disorders
Hypotension	15/287 (5.2%)		6/288 (2.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Results of Study shall not be published without prior express written consent and approval of Sponsor. Sponsor has right to change proposed publication and/or prohibit publication and Contractor must comply with requirements of Sponsor.

Results Point of Contact

Name/Title	Howard Kessler
Organization	Daiichi Sankyo, Inc
Phone	732-590-5032
Email	hmkessler@dsi.com

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00141453

Other Study ID Numbers:

ORIENT

First Posted:

Sep 1, 2005

Last Update Posted:

May 10, 2011

Last Verified:

May 1, 2011

ORIENT: Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact