Efficacy and Safety Study on Menatetrenone in the Treatment of Postmenopausal Osteoporosis Women

• Sponsor: Eisai Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00165698
• Collaborator: (none)
• Enrollment: 240
• Locations: 5
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 48
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

To determine the effect and safety of menatetrenone on treatment of postmenopausal osteoporosis comparing with alfacalcidol.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: menatetranone; Drug: alfacalcidol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety Study on Menatetrenone in the Treatment of Postmenopausal Osteoporosis Women
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Jan 1, 2007
• Actual Study Completion Date: Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1	Drug: menatetranone; 15 mg three times a day orally for 12 months
Active Comparator: 2	Drug: alfacalcidol; 0.25 μg twice a day orally for 12 months

Outcome Measures

Primary Outcome Measures

1. Bone Mineral Density BMD (Percentage) Change in Lumber Spine After 12 Months [Baseline and 12 months]

2. Bone Mineral Density BMD (Percentage) Change in Collum Femoris After 12 Months [Baseline and 12 months]

3. Bone Mineral Density BMD (Percentage) Change in Trochiter After 12 Months [Baseline and 12 months]

Secondary Outcome Measures

1. Bone Mineral Content BMC (Percentage) Change in Lumber Spine After 12 Months [Baseline and 12 months]

2. Bone Mineral Content BMC (Percentage) Change in Collum Femoris After 12 Months [Baseline and 12 months]

3. Bone Biomarker Osteocalcin (OC) Percentage Change After 12 Months [Baseline and 12 months]

4. Bone Biomarker Undercarboxylated Osteocalcin (UCOC) Percentage Change After 12 Months [Baseline and 12 months]

5. Bone Biomarker Undercarboxylated Osteocalcin/Osteocalcin (UCOC/OC) Percentage Change After 12 Months [Baseline and 12 months]

6. New Fracture and Fall [12 months]

7. Height (Meter) [Baseline and 12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 75 Years
• Sexes Eligible for Study: Female

Inclusion criteria :

• Postmenopausal women with menopause duration more than 5 years and with age between 45-75 years old (menopausal age ≥40), or if hysterectomy operated before natural menopause, the age of women between 60-75 years old.

• Subject with BMD (L2-4 or neck of femur) being more than 2 Standard Deviation (SD) below the young female adult mean (According to the standard of each center)

• BMI between 18 kg/m2-30 kg/m2.

• The anatomic structure of lumbar spine must be available for Dual-energy X-ray Absorptiometry (DEXA) examination, patient with serious scoliosis, bone trauma or sequela after orthopedics surgery, which makes BMD measurement difficult, should be excluded

• Subject who have given informed consent prior to participation in the trial and who undertake to comply with the protocol.

Exclusion Criteria

• Subject with conditions that are considered to effect osteoporosis, such as clear definite diabetes mellitus, rheumatoid arthritis, rheumatoid arthritis, hyperparathyroidism or other bone metabolic diseases.

• Subjects who have received treatment with active-type vitamin D3 preparation, other vitamin D preparations (>1000IU per day）, calcitonin, corticosteroid hormone, androgen, estrogen, other hormone, vitamin K preparation, in the 3 months prior to inanition of this study; Subjects who have received treatment with bisphosphonate preparation or Sodium Fluoride in the 1 year prior to inanition of this study; Subjects who have received treatment with Selective Estrogen Receptor Modulator (SERM) in the 6 months prior to inanition of this study

• Concurrent serious renal disease, hepatic disease, uncontrolled hypertension （≥150/100mmHg）, symptomatic ischemic heart disease, cerebral infarction or arteriosclerosis obliterans.

• Cancer history within 5 years.

• Subjects who take antacid containing aluminum in the preparation, warfarin or thrombolytic agents.

• Subject with any known abnormality in laboratory tests, which is deemed to be clinically significant by the investigator, which include:

• Serum alkaline phosphatace (ALP) > upper normal limit 10% (calculated according to the range of normal values of each center);

• Glutamic Oxalacetic Transaminase (AST)/ Glutamic Pyruvic Transaminase (ALT) > upper normal limit 50％(calculated according to the range of normal values of each center);

• Serum creatinine >1.5mg/dL (133μmol/L);

• Blood-fasting sugar ≥ 7mmol/L (126mg/L)

• Inability of subject to return for scheduled visits or to comply with any other aspect of the protocol.

• Subject who, in the opinion of the investigator, are poor medical candidates or pose any other risk for therapy with an investigational drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Hospital	Beijing		China
2	Chinese PLA General Hospital	Beijing		China
3	Peking Union Medical College Hospital	Beijing		China
4	Hua Dong Hospital	Shanghai		China
5	The Sixth People's Hospital affiliated to Shanghai Jiaopong University	Shanghai		China

Sponsors and Collaborators

• Eisai Co., Ltd.

Investigators

• Study Director: Hong Di, Eisai China Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00165698
• Other Study ID Numbers: AS-012 (GLA-CHN-05-01)
• First Posted: Sep 14, 2005
• Last Update Posted: Jul 22, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by , ,: Postmenopausal; osteoporosis
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Alfacalcidol; Hydroxycholecalciferols

Study Results

Participant Flow

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Period Title: Overall Study
STARTED	120	120
COMPLETED	112	105
NOT COMPLETED	8	15

Baseline Characteristics

Arm/Group Title	Menatetrenone	Alfacalcidol	Total
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months	Total of all reporting groups
Overall Participants	112	108	220
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.6 (6.1)	64.2 (6.3)	64.4 (6.2)
Sex: Female, Male (Count of Participants)
Female	112 100%	108 100%	220 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Asian	112 100%	108 100%	220 100%
Region of Enrollment (participants) [Number]
China	112 100%	108 100%	220 100%

Outcome Measures

1. Primary Outcome

Title	Bone Mineral Density BMD (Percentage) Change in Lumber Spine After 12 Months
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	105
Median (Full Range) [percentage of BMD]	1.22	2.17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menatetrenone, Alfacalcidol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Symbols rank sum test
	Comments

2. Primary Outcome

Title	Bone Mineral Density BMD (Percentage) Change in Collum Femoris After 12 Months
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	105
Median (Full Range) [percentage of BMD]	0.76	0.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menatetrenone, Alfacalcidol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Symbols rank sum test
	Comments

3. Primary Outcome

Title	Bone Mineral Density BMD (Percentage) Change in Trochiter After 12 Months
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	105
Median (Full Range) [percentage of BMD]	2.66	1.76

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menatetrenone, Alfacalcidol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Symbols rank sum test
	Comments

4. Secondary Outcome

Title	Bone Mineral Content BMC (Percentage) Change in Lumber Spine After 12 Months
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	103
Median (Full Range) [percentage of BMC]	2.39	2.81

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menatetrenone, Alfacalcidol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.869
	Comments
	Method	symbols rank sum test
	Comments

5. Secondary Outcome

Title	Bone Mineral Content BMC (Percentage) Change in Collum Femoris After 12 Months
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	103
Median (Full Range) [percentage of BMC]	1.58	0.95

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menatetrenone, Alfacalcidol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.174
	Comments
	Method	symbols rank sum test
	Comments

6. Secondary Outcome

Title	Bone Biomarker Osteocalcin (OC) Percentage Change After 12 Months
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	104
Median (Inter-Quartile Range) [percentage of OC]	-38.67	-25.77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menatetrenone, Alfacalcidol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.000
	Comments
	Method	symbols rank sum test
	Comments

7. Secondary Outcome

Title	Bone Biomarker Undercarboxylated Osteocalcin (UCOC) Percentage Change After 12 Months
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	104
Median (Inter-Quartile Range) [percentage of UCOC]	-82.27	-34.83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menatetrenone, Alfacalcidol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.000
	Comments
	Method	symbols rank sum test
	Comments

8. Secondary Outcome

Title	Bone Biomarker Undercarboxylated Osteocalcin/Osteocalcin (UCOC/OC) Percentage Change After 12 Months
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	104
Median (Inter-Quartile Range) [percentage of UCOC/OC]	-70.64	-8.47

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menatetrenone, Alfacalcidol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.000
	Comments
	Method	symbols rank sum test
	Comments

9. Secondary Outcome

Title	New Fracture and Fall
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	105
fracture	2 1.8%	4 3.7%
fall	13 11.6%	10 9.3%

10. Secondary Outcome

Title	Height (Meter)
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS)

Arm/Group Title	Menatetrenone	Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months	0.25 μg b.i.d. orally for 12 months
Measure Participants	108	105
Baseline	1.54 (0.05)	1.55 (0.05)
At 12 months	1.54 (0.06)	1.55 (0.05)

Adverse Events

Adverse Event Reporting Description	Safety Population
Arm/Group Title	Menatetrenone		Alfacalcidol
Arm/Group Description	15 mg t.i.d. orally for 12 months		0.25 μg b.i.d. orally for 12 months
All Cause Mortality
	Menatetrenone		Alfacalcidol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Menatetrenone		Alfacalcidol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/117 (6.8%)		6/118 (5.1%)
Cardiac disorders
Chest distress	1/117 (0.9%)		0/118 (0%)
Coronary artery disease	2/117 (1.7%)		0/118 (0%)
Angina	1/117 (0.9%)		0/118 (0%)
Arrhythmia	1/117 (0.9%)		0/118 (0%)
Endocrine disorders
Parathyroid malignant tumor	0/117 (0%)		1/118 (0.8%)
NTT	1/117 (0.9%)		0/118 (0%)
Goiter	1/117 (0.9%)		1/118 (0.8%)
Musculoskeletal and connective tissue disorders
Bone fracture	2/117 (1.7%)		0/118 (0%)
Tendon damage	1/117 (0.9%)		0/118 (0%)
Nervous system disorders
Dizziness	0/117 (0%)		1/118 (0.8%)
Reproductive system and breast disorders
Breast cancer	0/117 (0%)		1/118 (0.8%)
Skin and subcutaneous tissue disorders
Skin damage	1/117 (0.9%)		0/118 (0%)
Surgical and medical procedures
Nerve sheath tumor surgery	0/117 (0%)		1/118 (0.8%)
Uterus resection	1/117 (0.9%)		0/118 (0%)
Vascular disorders
Hypertension	0/117 (0%)		1/118 (0.8%)
Other (Not Including Serious) Adverse Events
	Menatetrenone		Alfacalcidol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/117 (69.2%)		74/118 (62.7%)
Cardiac disorders
Abnormal Cardiovascular system	16/117 (13.7%)		10/118 (8.5%)
Heart rate and rhythm disorders	9/117 (7.7%)		8/118 (6.8%)
Gastrointestinal disorders
Gastrointestinal disorders	37/117 (31.6%)		32/118 (27.1%)
General disorders
Systemic anomalies	8/117 (6.8%)		6/118 (5.1%)
Others	27/117 (23.1%)		25/118 (21.2%)
Hepatobiliary disorders
Abnormal liver system	7/117 (6%)		6/118 (5.1%)
Metabolism and nutrition disorders
Metabolism and nutrition disorders	8/117 (6.8%)		3/118 (2.5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal system abnormalities	20/117 (17.1%)		18/118 (15.3%)
Nervous system disorders
Central and peripheral nervous system abnormalities	10/117 (8.5%)		9/118 (7.6%)
Renal and urinary disorders
Urinary system abnormalities	12/117 (10.3%)		12/118 (10.2%)
Respiratory, thoracic and mediastinal disorders
Respiratory abnormalities	24/117 (20.5%)		35/118 (29.7%)
Skin and subcutaneous tissue disorders
Abnormal on skin and its subsidiary tissues	7/117 (6%)		5/118 (4.2%)

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.