A Study of Oral Recombinant Salmon Calcitonin (rsCT) to Prevent Postmenopausal Osteoporosis

• Sponsor: Tarsa Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01292187
• Collaborator: (none)
• Enrollment: 129
• Locations: 10
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 12.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The primary purpose of this study was to evaluate the efficacy of oral calcitonin (rsCT)tablets in the prevention of bone loss in postmenopausal women with lower bone mineral density at increased risk of fracture. The secondary purpose of this study was to determine if there is any food effect by comparing the efficacy and safety of oral calcitonin tablets administered at dinner or at bedtime.

Condition or Disease	Intervention/Treatment	Phase
Osteopenia	Drug: Oral calcitonin at dinnertime; Drug: Oral placebo at dinnertime; Drug: Oral calcitonin at bedtime; Drug: Oral placebo at bedtime	Phase 2

Detailed Description

This was a randomized, double-blind, placebo-controlled Phase 2 study conducted entirely in the US. The subjects were all post-menopausal women whose 10-year risk of major osteoporotic fracture was assessed using the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX®) algorithm within the first 3 visits. Eligible, consenting subjects were then enrolled and began a 2- week single-blind placebo run-in phase to determine tolerability. After the run-in phase, continuing subjects were randomized in a 2:1 ratio to receive oral calcitonin or placebo. All subjects took 600 mg calcium citrate and 1000 IU vitamin D once daily with breakfast beginning with the run-in phase. The duration of treatment including the run-in phase was 54 weeks. Bone mineral density (BMD) and C-terminal telopeptide of type 1 collagen (CTx-1) were determined at Baseline and Weeks 28 and 54 after randomization. The % change from baseline in lumbar spine BMD was calculated and compared: active to placebo. The change from baseline in plasma CTx-1 was also calculated and compared likewise.

To confirm that there is no effect of meal timing on this product, subjects in both arms were further randomized to take the active or placebo on an empty stomach at bedtime or with the meal at dinnertime.

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-blind, Placebo-controlled Clinical Trial Evaluating the Safety and Efficacy of Oral Recombinant Salmon Calcitonin (rsCT) in the Prevention of Postmenopausal Osteoporosis in Women at Increased Risk of Fracture
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral calcitonin at dinner-or bedtime Intervention: Oral calcitonin at dinnertime or oral calcitonin at bedtime. Postmenopausal subjects with osteopenia were treated for one year (also with vitamin D and calcium supplements) to determine if oral calcitonin tablets would prevent the loss of bone mineral density compared with placebo. Randomization to active or placebo was done 2:1. After randomization, further randomization was done to divide each arm into two groups, one in which dosing was at dinnertime and the other in which dosing was at bedtime to determine if food affected efficacy or safety.	Drug: Oral calcitonin at dinnertime; Oral calcitonin at dinnertime.; Other Names: Oral rsCT ; Drug: Oral calcitonin at bedtime; Oral calcitonin at bedtime; Other Names: Oral rsCT
Experimental: Oral placebo at dinner- or bedtime Intervention: oral placebo at dinnertime or oral placebo at bedtime	Drug: Oral placebo at dinnertime; Oral placebo at dinnertime.; Other Names: Placebo ; Drug: Oral placebo at bedtime; Oral placebo at bedtime; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage Change From Baseline to Week 54 of Lumbar Spine Bone Mineral Density of Active Compared to Placebo. [Baseline, Week 54]

Secondary Outcome Measures

1. Percentage Change From Baseline to Week 54 of Plasma CTx-1 Following rsCT Compared to Placebo. [Baseline, Week 54]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female and at least 45 years of age.

• Must have undergone the onset of spontaneous or surgical menopause more than 5 years prior to entry. Spontaneous menopause is defined as 12 months of spontaneous amenorrhea. Surgical menopause is defined as ≥ 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.

• Serum follicle-stimulating hormone (FSH) levels must be ≥ 30 mIU/mL.

• A body mass index (BMI) of not greater than 35 (BMI

=weight [kg]/height[m]2).

• Bone mineral density (BMD) T-score between -1.0 and - 2.5 at the total hip, femoral neck, trochanter, or lumbar spine.

• Additional risk factors such that the 10 year risk of a major osteoporotic fracture or hip fracture risk is at least as great as a 65-year-old woman of the same race and BMI of 25 kg/m2 as determined by the FRAX algorithm .

• No clinically significant abnormal findings in the medical history or physical exam that would preclude participation in the investigator's opinion.

• No clinically significant abnormal laboratory values at the screening assessment.

• Subjects must give written informed consent after reading the Subject Information and Consent Form and having had the opportunity to discuss the study with the investigator.

Exclusion Criteria:

• History of an osteoporotic fracture, defined as a fracture at the wrist, hip, or humerus occurring from a fall at standing height or less.

• BMD T-Score at any site ≤ -2.5.

• Current treatment (or within 3 months prior to randomization) with hormone replacement therapy.

• History of metabolic and other bone diseases, including osteogenesis imperfecta, osteomalacia, and Paget's disease.

• Vitamin D insufficiency defined as a 25 hydroxyvitamin D level < 20 ng/mL (50 nmol/L).

• Prior use of calcitonin, ever.

• Prior use of any bisphosphonate, ever.

• Prior use of denosumab, fluoride, or strontium, ever.

• Prior use of parathyroid hormone analogs, ever.

• Any condition or disease that may interfere with the ability to have a dual energy x-ray absorptiometry (DXA) scan or to evaluate a DXA scan, for example, severe osteoarthritis of the spine, spinal fusion, pedicle screws, history of vertebroplasty, or degenerative disease that results in insufficient number of evaluable lumbar vertebrae, bilateral hip replacements.

• Use of anabolic steroids or androgens within 6 months preceding randomization.

• Use of vitamin D metabolites and analogs, (e.g., calcitriol) within 3 months preceding randomization). Note: Vitamin D supplementation is not exclusionary.

• Use of estrogen or estrogen-related drugs (including selective estrogen receptor molecules), for example, tamoxifen, tibolone, or raloxifene within 3 months preceding randomization.

• Chronic systemic treatment with glucocorticoids.

• Clinically relevant abnormal history, physical findings, or laboratory values at the pre-study screening assessment that could interfere with the objectives of the study or the safety of the subject.

• Presence of acute or chronic illness or history of chronic illness which, in the judgment of the investigator, makes participation in the study medically inappropriate.

• Known acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) seropositivity.

• Uncontrolled hypertension, significant gastrointestinal abnormalities, uncontrolled diabetes mellitus, significant coronary heart disease, any psychotic mental illness, chronic allergic rhinitis, asthma, uncorrected endocrine dysfunction, or significantly impaired hepatic, respiratory, or renal function.

• Participation in any other clinical study within the previous month.

• History of drug or alcohol abuse, or intake of more than 30 units of alcohol weekly.

• Possibility that the subject will not cooperate with the requirements of the protocol.

• Known sensitivity to sCT.

• Shift workers-individuals who are at work during overnight hours.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Diablo Clinical Research, Inc.	Walnut Creek	California	United States	94598
2	Innovative Research of West Florida, Inc.	Clearwater	Florida	United States	33756
3	Bethesda Health Research	Bethesda	Maryland	United States	20817
4	Clinical Pharmacology Study Group	Worcester	Massachusetts	United States	01610
5	Michigan Bone and Mineral Clinic	Detroit	Michigan	United States	48236
6	The Osteoporosis Center at St. Luke's Hospital	Chesterfield	Missouri	United States	63107
7	Comprehensive Clinical Research	Berlin	New Jersey	United States	08009
8	University of Pittsburgh - Department of Neurology	Pittsburgh	Pennsylvania	United States	15213
9	Puget Sound Osteoporosis Center	Seattle	Washington	United States	98144
10	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53705

Sponsors and Collaborators

• Tarsa Therapeutics, Inc.

Investigators

• Study Director: David S. Krause, MD, Chief Medical Officer - Tarsa Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info.

Publications

None provided.

• Responsible Party: Tarsa Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01292187
• Other Study ID Numbers: TAR-01-201
• First Posted: Feb 9, 2011
• Last Update Posted: Sep 12, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Tarsa Therapeutics, Inc.: Osteoporosis; Osteopenia; Osteoporosis, Postmenopausal; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Salmon calcitonin; Calcitonin
• Additional relevant MeSH terms: Osteoporosis; Bone Diseases, Metabolic; Osteoporosis, Postmenopausal; Calcitonin; Salmon calcitonin; Calcitonin Gene-Related Peptide; Katacalcin

Study Results

Participant Flow

Recruitment Details	Subjects will be recruited from outpatient populations associated with health care centers that treat osteoporosis. Community advertising may also be used for those not associated with such centers. Recruitment began on 17 January 2011.
Pre-assignment Detail	All patients had a two-week single-blind oral placebo (at bedtime) run-in period before group assignment. This was to accustom the patients to the oral dose regimen prior to randomization

Arm/Group Title	Oral rsCT Tablets	Oral Placebo Tablets
Arm/Group Description	Tablets containing 200 μg of recombinant salmon calcitonin, for oral administration. At group assignment the first 60 patients were told to self-administer the tablets once daily at bedtime (Group 1). The remaining patients were told to self-administer once daily at dinner time (Group 2)to determine if there was any food effect. Randomization was done active:placebo, 2:1.	Identical appearing placebo tablets, without active ingredient At group assignment the first 60 patients were told to self-administer the tablets once daily at bedtime Group 1). The remaining patients enrolled were told to self-administer once daily at dinner time (Group 2)to determine if there was any food effect. Randomization was done active:placebo, 2:1.
Period Title: Overall Study
STARTED	86	43
COMPLETED	69	30
NOT COMPLETED	17	13

Baseline Characteristics

Arm/Group Title	rsCT Tablets	Placebo Tablets	Total
Arm/Group Description	Patients who received oral calcitonin as an active treatment	Patients who did not receive any active treatment, just placebo	Total of all reporting groups
Overall Participants	86	43	129
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	28 32.6%	14 32.6%	42 32.6%
>=65 years	58 67.4%	29 67.4%	87 67.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.5 (6.90)	66.6 (5.16)	67.2 (6.37)
Sex: Female, Male (Count of Participants)
Female	86 100%	43 100%	129 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2.3%	0 0%	2 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 2.3%	2 4.7%	4 3.1%
White	81 94.2%	41 95.3%	122 94.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.2%	0 0%	1 0.8%
Region of Enrollment (participants) [Number]
United States	86 100%	43 100%	129 100%
T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-1.15 (0.881)	-1.12 (0.864)	-1.14 (0.872)
FRAX Score (percent probability) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent probability]	11.87 (5.019)	11.57 (4.468)	11.77 (4.827)
LS BMD (grams per square centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams per square centimeter]	0.940 (0.106)	0.929 (0.907)	0.936 (0.102)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.81 (3.765)	26.77 (5.983)	26.13 (25.48)
CTx-1 (ng/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/L]	423.95 (219.419)	417 (119.882)	421.74 (193.638)

Outcome Measures

1. Primary Outcome

Title	Percentage Change From Baseline to Week 54 of Lumbar Spine Bone Mineral Density of Active Compared to Placebo.
Time Frame	Baseline, Week 54

Outcome Measure Data

Analysis Population Description

MITT population

Arm/Group Title	Oral Calcitonin Tablets	Oral Placebo Tablets
Arm/Group Description	Tablets containing 200 μg of recombinant salmon calcitonin, for oral administration. At group assignment the first 60 patients were told to self-administer the tablets once daily at bedtime (Group 1). The remaining patients were told to self-administer once daily at dinner time (Group 2)to determine if there was any food effect. Randomization was done active:placebo, 2:1.	Identical appearing placebo tablets, without active ingredient At group assignment the first 60 patients were told to self-administer the tablets once daily at bedtime Group 1). The remaining patients enrolled were told to self-administer once daily at dinner time (Group 2)to determine if there was any food effect. Randomization was done active:placebo, 2:1.
Measure Participants	74	35
Least Squares Mean (95% Confidence Interval) [percent change]	1.03	-0.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Calcitonin Tablets, Oral Placebo Tablets
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0265
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Percentage Change From Baseline to Week 54 of Plasma CTx-1 Following rsCT Compared to Placebo.
Time Frame	Baseline, Week 54

Outcome Measure Data

Analysis Population Description

MITT population

Arm/Group Title	Oral rsCT Tablets	Oral Placebo Tablets
Arm/Group Description	Tablets containing 200 μg of recombinant salmon calcitonin, for oral administration. At group assignment the first 60 patients were told to self-administer the tablets once daily at bedtime (Group 1). The remaining patients were told to self-administer once daily at dinner time (Group 2)to determine if there was any food effect. Randomization was done active:placebo, 2:1.	Identical appearing placebo tablets, without active ingredient At group assignment the first 60 patients were told to self-administer the tablets once daily at bedtime Group 1). The remaining patients enrolled were told to self-administer once daily at dinner time (Group 2)to determine if there was any food effect. Randomization was done active:placebo, 2:1.
Measure Participants	78	36
Least Squares Mean (95% Confidence Interval) [percent change]	-11.83	8.37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Calcitonin Tablets, Oral Placebo Tablets
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0340
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	1 year
Arm/Group Title	Oral rsCT Tablets		Oral Placebo Tablets
Arm/Group Description	Tablets containing 200 μg of recombinant salmon calcitonin, for oral administration. At group assignment the first 60 patients were told to self-administer the tablets once daily at bedtime (Group 1). The remaining patients were told to self-administer once daily at dinner time (Group 2)to determine if there was any food effect. Randomization was done active:placebo, 2:1.		Identical appearing placebo tablets, without active ingredient At group assignment the first 60 patients were told to self-administer the tablets once daily at bedtime Group 1). The remaining patients enrolled were told to self-administer once daily at dinner time (Group 2)to determine if there was any food effect. Randomization was done active:placebo, 2:1.
All Cause Mortality
	Oral rsCT Tablets		Oral Placebo Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oral rsCT Tablets		Oral Placebo Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/86 (7%)		2/43 (4.7%)
Cardiac disorders
Pericardial effusions	1/86 (1.2%)	1	0/43 (0%)	0
General disorders
Pyrexia	1/86 (1.2%)	1	0/43 (0%)	0
Hepatobiliary disorders
Hepatitis acute	1/86 (1.2%)	1	0/43 (0%)	0
Infections and infestations
Sepsis	1/86 (1.2%)	1	0/43 (0%)	0
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	2/86 (2.3%)	3	0/43 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified	3/86 (3.5%)	3	2/43 (4.7%)	2
Other (Not Including Serious) Adverse Events
	Oral rsCT Tablets		Oral Placebo Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/86 (38.4%)		15/43 (34.9%)
Gastrointestinal disorders
Abdominal pain	6/86 (7%)	9	6/43 (14%)	9
Abdominal discomfort	9/86 (10.5%)	11	1/43 (2.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	10/86 (11.6%)	11	1/43 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	8/86 (9.3%)	10	7/43 (16.3%)	8

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.