2MD-3H-2B: Phase 2 Safety and Efficacy Study of a Vitamin D Compound (DP001) in Postmenopausal Women With Low Bone Mineral Density

• Sponsor: Deltanoid Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00715676
• Collaborator: (none)
• Enrollment: 157
• Locations: 9
• Arms: 3
• Duration (Months): 22.1
• Patients Per Site: 17.4
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This study will evaluate the effect of a 1-year administration of the vitamin D analog 2-methylene-19-nor-(20S)-1alpha, 25-dihydroxyvitamin D3 (DP001) on bone mineral density (BMD), safety, and tolerability.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: Placebo; Drug: DP001	Phase 2

Detailed Description

DP001 is a vitamin D analog that has been shown to stimulate bone formation in pre-clinical studies. In a Phase 1B study of postmenopausal women, an increase in the bone formation marker, osteocalcin, was evident without an increase in serum calcium. The aim of this study is to determine if 1-year administration of DP001 to postmenopausal women with osteopenia results in a significant increase in BMD at doses that are safe and well tolerated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 157 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Double-blind, Randomized, Placebo-Controlled, Daily-dose, Proof-of-concept Study of a Vitamin D Compound in Postmenopausal Women With Osteopenia
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Group 1	Drug: Placebo; oral, once daily
Experimental: Group 2 220 ng	Drug: DP001; oral, once daily; Other Names: 2-methylene-19-nor-(20S)-1a, 25-dihydroxyvitamin D3 2MD
Experimental: Group 3 440 ng	Drug: DP001; oral, once daily; Other Names: 2-methylene-19-nor-(20S)-1a, 25-dihydroxyvitamin D3 2MD

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 [Baseline and Week 52]

   Percent change in lumbar spine BMD (relative to baseline) at Week 52

Secondary Outcome Measures

1. Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 52 [Baseline and Week 52]

   The percent change in hip BMD (relative to baseline) at Week 52

2. Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Week 52 [Baseline and Week 52]

   Percent change in femoral neck BMD (relative to baseline) at Week 52

3. Percent Change From Baseline in Trochanter Bone Mineral Density (BMD) at Week 52 [Baseline and Week 52]

   Percent change in trochanter BMD (relative to baseline) at Week 52

4. Change From Baseline in Serum Calcium Levels at Week 52 [Baseline and Week 52]

   Change in serum calcium value (relative to baseline) at Week 52

5. Percent Change From Baseline in Serum Bone Markers at Week 26 [Baseline and Week 26]

   Percent change from baseline at Week 26

6. Number of Subjects With at Least 1 Treatment-emergent Adverse Event [1 year]

   To assess safety and tolerability, the number of subjects in each treatment group who had one or more adverse events recorded after the beginning of study drug administration were determined.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Postmenopausal female subjects, defined as amenorrheic for at least 5 years

• Body Mass Index of 18 to 35

• Osteopenic

• Generally healthy

• Informed consent

Exclusion Criteria

• History or evidence of acute or unstable chronic hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, or neurologic diseases

• Current or recent treatment with any medications or products affecting vitamin D metabolism, calcium balance, bone turnover, or an investigational drug therapy

• 12-lead electrocardiogram demonstrating QTc (QT interval corrected for heart rate)

450 milliseconds at screening

• Abnormal creatinine clearance

• Elevated urinary calcium levels

• Vitamin D deficiency

• Excessive dietary calcium or vitamin D intake

• Current use of any illicit drug and/or history of alcohol abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boling Clinical Trials	Upland	California	United States	91786
2	Indiana School of Medicine University Hospital	Indianapolis	Indiana	United States	46202
3	Bethesda Health Research	Bethesda	Maryland	United States	20817
4	Creighton University Bone Metabolism Unit	Omaha	Nebraska	United States	68131
5	New Mexico Clinical Research and Osteoporosis Center	Albuquerque	New Mexico	United States	87106
6	Winthrop University Hospital Bone Mineral Research Center	Mineola	New York	United States	11501
7	Helen Hayes Hospital Clinical Research Center	West Haverstraw	New York	United States	10993
8	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
9	University of Wisconsin-Madison Osteoporosis Clinical Research	Madison	Wisconsin	United States	53705

Sponsors and Collaborators

• Deltanoid Pharmaceuticals

Investigators

• Study Director: Wendy A Bedale, Ph.D., Deltanoid Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ke HZ, Qi H, Crawford DT, Simmons HA, Xu G, Li M, Plum L, Clagett-Dame M, DeLuca HF, Thompson DD, Brown TA. A new vitamin D analog, 2MD, restores trabecular and cortical bone mass and strength in ovariectomized rats with established osteopenia. J Bone Miner Res. 2005 Oct;20(10):1742-55. Epub 2005 Jun 13.
• Plum LA, Fitzpatrick LA, Ma X, Binkley NC, Zella JB, Clagett-Dame M, DeLuca HF. 2MD, a new anabolic agent for osteoporosis treatment. Osteoporos Int. 2006;17(5):704-15. Epub 2006 Feb 21.
• Shevde NK, Plum LA, Clagett-Dame M, Yamamoto H, Pike JW, DeLuca HF. A potent analog of 1alpha,25-dihydroxyvitamin D3 selectively induces bone formation. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13487-91. Epub 2002 Oct 8.

• ClinicalTrials.gov Identifier: NCT00715676
• Other Study ID Numbers: Deltanoid 2MD-3H-2B
• First Posted: Jul 15, 2008
• Last Update Posted: Jan 11, 2010
• Last Verified: Dec 1, 2009

• Keywords provided by , ,: Osteoporosis; 2-methylene-19-nor-(20S)-1a, 25-dihydroxyvitamin D3; Vitamin D; Bone Density Conservation Agents; Bone Regeneration
• Additional relevant MeSH terms: Osteoporosis; Dihydroxycholecalciferols

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled from 5 March 2007 to 19 December 2007 at 9 centers within the United States.

Arm/Group Title	Placebo	220 ng of Vitamin D Analog (DP001)	440 ng DP001
Arm/Group Description	Placebo soft gel capsules, oral, once daily	220 ng DP001 soft gel capsules, oral, once daily DP001 is also known as 2-methylene-19-nor-(20S)-1alpha, 25-dihydroxyvitamin D3.	440 ng DP001 soft gel capsules, oral, once daily
Period Title: Overall Study
STARTED	49	54	53
COMPLETED	43	43	21
NOT COMPLETED	6	11	32

Baseline Characteristics

Arm/Group Title	Placebo	220 ng DP001	440 ng DP001	Total
Arm/Group Description	Placebo soft gel capsules, oral, once daily	220 ng DP001 soft gel capsules, oral, once daily	440 ng DP001 soft gel capsules, oral, once daily	Total of all reporting groups
Overall Participants	49	54	53	156
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.1 (6.5)	61.6 (5.5)	61.9 (5.3)	61.5 (5.8)
Sex: Female, Male (Count of Participants)
Female	49 100%	54 100%	53 100%	156 100%
Male	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52
Description	Percent change in lumbar spine BMD (relative to baseline) at Week 52
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Full Analysis Set, which included all subjects who received at least one dose of study drug. Multiple imputation was used for missing data.

Arm/Group Title	Placebo	220 ng DP001	440 ng DP001
Arm/Group Description	Placebo soft gel capsules, oral, once daily	220 ng DP001 soft gel capsules, oral, once daily	440 ng DP001 soft gel capsules, oral, once daily
Measure Participants	49	54	53
Mean (Standard Deviation) [Percent change]	-0.537 (2.545)	-0.174 (2.820)	0.309 (3.904)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 220 ng DP001
	Comments	A sample size of 49 per treatment group was calculated to have at least 90% power to detect a 2% or greater increase over placebo assuming the following: (1) a standard deviation of the percent change of 2.75% (2) a dropout rate of 30%, and (3) one-sided 0.05 level of significance
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.641
	Comments	The Hochberg method was used to compare dose groups to placebo and control the Type 1 error rate.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 440 ng DP001
	Comments	A sample size of 49 per treatment group was calculated to have at least 90% power to detect a 2% or greater increase over placebo assuming the following: (1) a standard deviation of the percent change of 2.75% (2) a dropout rate of 30%, and (3) one-sided 0.05 level of significance
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.243
	Comments	The Hochberg method was used to compare dose groups to placebo and control the Type 1 error rate.
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 52
Description	The percent change in hip BMD (relative to baseline) at Week 52
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

This analysis was conducted on the Full Analysis Set, which included all randomized subjects who received at least one dose of study drug. Multiple imputation was used for missing data.

Arm/Group Title	Placebo	220 ng DP001	440 ng DP001
Arm/Group Description	Placebo soft gel capsules, oral, once daily	220 ng DP001 soft gel capsules, oral, once daily	440 ng DP001 soft gel capsules, oral, once daily
Measure Participants	49	54	53
Mean (Standard Deviation) [Percent Change]	-0.315 (1.894)	-0.540 (1.782)	-0.887 (1.833)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 220 ng DP001
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.778
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 440 ng DP001
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.173
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Week 52
Description	Percent change in femoral neck BMD (relative to baseline) at Week 52
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Full Analysis Set, which included all subjects who received at least one dose of study drug. Multiple imputation was used for missing data.

Arm/Group Title	Placebo	220 ng DP001	440 ng DP001
Arm/Group Description	Placebo soft gel capsules, oral, once daily	220 ng DP001 soft gel capsules, oral, once daily	440 ng DP001 soft gel capsules, oral, once daily
Measure Participants	49	54	53
Mean (Standard Deviation) [Percent change]	-0.428 (2.511)	-1.085 (3.150)	-0.680 (2.507)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 220 ng DP001
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.395
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 440 ng DP001
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.523
	Comments
	Method	ANOVA
	Comments

4. Secondary Outcome

Title	Percent Change From Baseline in Trochanter Bone Mineral Density (BMD) at Week 52
Description	Percent change in trochanter BMD (relative to baseline) at Week 52
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Full Analysis Set, which included all subjects who received at least one dose of study drug. Multiple imputation was used for missing data.

Arm/Group Title	Placebo	220 ng DP001	440 ng DP001
Arm/Group Description	Placebo soft gel capsules, oral, once daily	220 ng DP001 soft gel capsules, oral, once daily	440 ng DP001 soft gel capsules, oral, once daily
Measure Participants	49	54	53
Mean (Standard Deviation) [Percent change]	-0.375 (2.604)	-0.341 (2.565)	-0.941 (2.554)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 220 ng DP001
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.928
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 440 ng DP001
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.124
	Comments
	Method	ANOVA
	Comments

5. Secondary Outcome

Title	Change From Baseline in Serum Calcium Levels at Week 52
Description	Change in serum calcium value (relative to baseline) at Week 52
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

This analysis was done for all subjects for whom both baseline and Week 52 data was available.

Arm/Group Title	Placebo	220 ng DP001	440 ng DP001
Arm/Group Description	Placebo soft gel capsules, oral, once daily	220 ng DP001 soft gel capsules, oral, once daily	440 ng DP001 soft gel capsules, oral, once daily
Measure Participants	43	43	21
Mean (Standard Deviation) [mg/dL]	-0.06 (0.268)	0.11 (0.286)	0.29 (0.243)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 220 ng DP001
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.173
	Confidence Interval	() 90%; 0.164 to 0.181
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 440 ng DP001
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.582
	Confidence Interval	() 90%; 0.573 to 0.591
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percent Change From Baseline in Serum Bone Markers at Week 26
Description	Percent change from baseline at Week 26
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

Analyses were performed using subjects for whom both Baseline and Week 26 samples were available.

Arm/Group Title	Placebo	220 ng DP001	440 ng DP001
Arm/Group Description	Placebo soft gel capsules, oral, once daily	220 ng DP001 soft gel capsules, oral, once daily	440 ng DP001 soft gel capsules, oral, once daily
Measure Participants	45	45	29
Serum C-telopeptide cross-links of type 1 collagen	4.5 (25.4)	13.8 (32.4)	54.5 (54.2)
Osteocalcin	3.8 (19.4)	22.4 (38.0)	80.3 (73.3)
Procollagen type 1 N-propeptide	1.0 (29.5)	11.8 (40.7)	9.2 (33.4)

7. Secondary Outcome

Title	Number of Subjects With at Least 1 Treatment-emergent Adverse Event
Description	To assess safety and tolerability, the number of subjects in each treatment group who had one or more adverse events recorded after the beginning of study drug administration were determined.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The participants for this analysis included all randomized subjects who received a dose of study drug.

Arm/Group Title	Placebo	220 ng DP001	440 ng DP001
Arm/Group Description	Placebo soft gel capsules, oral, once daily	220 ng DP001 soft gel capsules, oral, once daily	440 ng DP001 soft gel capsules, oral, once daily
Measure Participants	49	54	53
Number [Participants]	41 83.7%	45 83.3%	46 86.8%

Adverse Events

Time Frame	Adverse events were collected for a period of 1 year for subjects completing the study, and through study discontinuation for subjects who discontinued early.
Adverse Event Reporting Description	Adverse events were assessed by investigator assessment at subject visits and regular laboratory testing.
Arm/Group Title	Placebo		220 ng DP001		440 ng DP001
Arm/Group Description	Placebo soft gel capsules, oral, once daily		220 ng DP001 soft gel capsules, oral, once daily		440 ng DP001 soft gel capsules, oral, once daily
All Cause Mortality
	Placebo		220 ng DP001		440 ng DP001
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		220 ng DP001		440 ng DP001
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/49 (2%)		1/54 (1.9%)		3/53 (5.7%)
Metabolism and nutrition disorders
Hypercalcaemia	0/49 (0%)	0	1/54 (1.9%)	1	3/53 (5.7%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer	1/49 (2%)	1	0/54 (0%)	0	0/53 (0%)	0
Renal and urinary disorders
Renal failure acute	0/49 (0%)	0	1/54 (1.9%)	1	0/53 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		220 ng DP001		440 ng DP001
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/49 (77.6%)		37/54 (68.5%)		44/53 (83%)
Gastrointestinal disorders
Abdominal pain upper	2/49 (4.1%)		2/54 (3.7%)		4/53 (7.5%)
Constipation	5/49 (10.2%)		3/54 (5.6%)		6/53 (11.3%)
Diarrhoea	5/49 (10.2%)		1/54 (1.9%)		3/53 (5.7%)
Dyspepsia	6/49 (12.2%)		5/54 (9.3%)		2/53 (3.8%)
Nausea	5/49 (10.2%)		2/54 (3.7%)		6/53 (11.3%)
Stomach discomfort	4/49 (8.2%)		0/54 (0%)		3/53 (5.7%)
Vomiting	3/49 (6.1%)		0/54 (0%)		2/53 (3.8%)
General disorders
Fatigue	1/49 (2%)		3/54 (5.6%)		6/53 (11.3%)
Pyrexia	3/49 (6.1%)		0/54 (0%)		1/53 (1.9%)
Immune system disorders
Seasonal allergy	1/49 (2%)		3/54 (5.6%)		1/53 (1.9%)
Infections and infestations
Bronchitis	3/49 (6.1%)		0/54 (0%)		0/53 (0%)
Gastroenteritis viral	3/49 (6.1%)		1/54 (1.9%)		1/53 (1.9%)
Influenza	4/49 (8.2%)		1/54 (1.9%)		4/53 (7.5%)
Nasopharyngitis	10/49 (20.4%)		11/54 (20.4%)		6/53 (11.3%)
Upper respiratory tract infection	3/49 (6.1%)		1/54 (1.9%)		4/53 (7.5%)
Urinary tract infection	5/49 (10.2%)		2/54 (3.7%)		1/53 (1.9%)
Investigations
Blood creatinine increased	0/49 (0%)		1/54 (1.9%)		4/53 (7.5%)
Metabolism and nutrition disorders
Anorexia	3/49 (6.1%)		0/54 (0%)		1/53 (1.9%)
Hypercalcaemia	0/49 (0%)		2/54 (3.7%)		13/53 (24.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/49 (14.3%)		6/54 (11.1%)		7/53 (13.2%)
Back pain	3/49 (6.1%)		2/54 (3.7%)		8/53 (15.1%)
Muscle spasms	3/49 (6.1%)		2/54 (3.7%)		5/53 (9.4%)
Myalgia	0/49 (0%)		2/54 (3.7%)		3/53 (5.7%)
Pain in extremity	5/49 (10.2%)		3/54 (5.6%)		3/53 (5.7%)
Nervous system disorders
Headache	4/49 (8.2%)		7/54 (13%)		9/53 (17%)
Psychiatric disorders
Insomnia	2/49 (4.1%)		1/54 (1.9%)		3/53 (5.7%)
Renal and urinary disorders
Dysuria	0/49 (0%)		0/54 (0%)		4/53 (7.5%)
Hypercalciuria	0/49 (0%)		7/54 (13%)		12/53 (22.6%)
Respiratory, thoracic and mediastinal disorders
Cough	1/49 (2%)		3/54 (5.6%)		1/53 (1.9%)
Pharyngolaryngeal pain	4/49 (8.2%)		3/54 (5.6%)		3/53 (5.7%)
Vascular disorders
Hypertension	4/49 (8.2%)		1/54 (1.9%)		1/53 (1.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.