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Trial record 6 of 231 for:    CALCITONIN SALMON

A Study Comparing Oral Calcitonin to Nasal Spray Calcitonin in Postmenopausal Osteoporotic Women (ORACAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00959764
Recruitment Status : Completed
First Posted : August 17, 2009
Results First Posted : November 19, 2013
Last Update Posted : November 19, 2013
Sponsor:
Information provided by (Responsible Party):
Tarsa Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Osteoporosis, Postmenopausal
Interventions Drug: Oral Calcitonin Tablets
Drug: Intranasal Calcitonin
Drug: Placebo tablets and placebo intranasal spray
Enrollment 565
Recruitment Details Patients were recruited from clinics in the USA,UK,Poland, Bulgaria, Hungary, and Republic of South Africa.
Pre-assignment Details Unequal randomization was used for the study, with patients being assigned after inclusion/exclusion criteria were met.
Arm/Group Title Oral Calcitonin Nasal Calcitonin Placebo
Hide Arm/Group Description Patients who only received oral calcitonin as an active treatment Patients who only received nasal calcitonin as active treatment Patients who did not receive any active treatment
Period Title: Overall Study
Started 271 185 109
Completed 176 128 73
Not Completed 95 57 36
Arm/Group Title Oral Calcitonin Nasal Calcitonin Placebo Total
Hide Arm/Group Description Patients who only received oral calcitonin as an active treatment Patients who only received nasal calcitonin as active treatment Patients who did not receive any active treatment Total of all reporting groups
Overall Number of Baseline Participants 271 185 109 565
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 271 participants 185 participants 109 participants 565 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
115
  42.4%
77
  41.6%
39
  35.8%
231
  40.9%
>=65 years
156
  57.6%
108
  58.4%
70
  64.2%
334
  59.1%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 271 participants 185 participants 109 participants 565 participants
66.5  (7.6) 66.4  (7.0) 66.5  (8.0) 66.5  (7.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 271 participants 185 participants 109 participants 565 participants
Female
271
 100.0%
185
 100.0%
109
 100.0%
565
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 271 participants 185 participants 109 participants 565 participants
United States 35 24 12 71
Hungary 29 16 9 54
Poland 59 45 33 137
South Africa 52 33 14 99
Bulgaria 21 15 9 45
United Kingdom 75 52 32 159
1.Primary Outcome
Title Percent Change From Baseline in Bone Mineral Density (BMD) of Axial Lumbar Spine
Hide Description Bone Mineral Density is measured by Dual-Energy X-ray Absorptiometry (DXA) body scans. Two scans were taken for each timepoint(baseline, week 24 and week 48) and the mean of the two values was entered. The primary outcome timepoint was 48 weeks, but if a patient did not complete the full study, then the 24 week BMD value was used as Last Observation Carried Forward. The percentage change from the baseline value, set as 0%, was recorded as the primary outcome measure.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who were randomized, received treatment, and had at least one post-baseline BMD value measured at least 154 days after randomization.
Arm/Group Title Oral Calcitonin Nasal Calcitonin Placebo
Hide Arm/Group Description:
Patients who were provided active oral calcitonin and placebo nasal medication in a blinded fashion.
Patients who were provided active nasal calcitonin and placebo oral medication in a blinded fashion.
Patients who were provided nasal and oral placebo medication in a blinded fashion
Overall Number of Participants Analyzed 189 140 82
Least Squares Mean (Standard Deviation)
Unit of Measure: Percentage increase from baseline
1.53  (3.17) 0.76  (2.91) 0.47  (3.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Calcitonin, Nasal Calcitonin, Placebo
Comments The overall analysis across groups was an Analysis of Covariance where the study was powered to 80% with an assumption of a standard deviation of 2.5% and a two-sided 5% level of significance. For each treatment group, the BMD at 48 weeks was compared with the BMD at baseline and a % increase was calculated (baseline = 0%). This difference was subjected to the t-test. Two-sided P-value is less than or equal to 0.05 and was not adjusted as multiple comparisons were not done.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

Assumed placebo-adjusted effect for both active treatment groups (% increase in BMD)was 1.56% and that the placebo adjusted effect for the rsCT tablets must be at least 0.5 times the placebo adjusted effect for the calcitonin nasal spray (active control treatment group). The null hypothesis to be tested was:

[Mean(oral) – Mean(placebo)] - 0.5 x [Mean(nasal) – Mean(placebo)] < 0. Reference Pigeot, et al. 2003

Statistical Test of Hypothesis P-Value 0.002
Comments The P-value was not adjusted for multiple comparisons. The a priori threshold for statistical significance was <0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.08 to 1.45
Parameter Dispersion
Type: Standard Deviation
Value: 2.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Plasma C-terminal Telopeptide of Collagen 1 (CTx-1)
Hide Description Change from baseline in plasma CTx-1 at 24 and 48 weeks. CTx-1 is an accepted plasma biomarker as evidence of an effect on bone resorption and the effect of oral calcitonin was compared to that of intranasal calcitonin, both vs placebo.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population
Arm/Group Title Oral Calcitonin Nasal Calcitonin Placebo
Hide Arm/Group Description:
Patients who only received oral calcitonin as an active treatment
Patients who only received nasal calcitonin as active treatment
Patients who did not receive any active treatment
Overall Number of Participants Analyzed 184 135 78
Least Squares Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
-42.93  (41.99) -24.64  (41.61) -21.09  (62.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Calcitonin, Nasal Calcitonin, Placebo
Comments Same as for Primary Outcome
Type of Statistical Test Non-Inferiority or Equivalence
Comments Same as for Primary Outcome
Statistical Test of Hypothesis P-Value 0.0006
Comments P-value not adjusted for multiple comparisons; a priori threshold for significance was 0.05
Method ANCOVA
Comments 95% confidence interval not calculated
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -21.84
Parameter Dispersion
Type: Standard Deviation
Value: 41.99
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Plasma CTx-1 From Baseline
Hide Description Percent change from baseline of plasma CTx-1 at end of study=48 weeks
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population
Arm/Group Title Oral Calcitonin Nasal Calcitonin Placebo
Hide Arm/Group Description:
Patients who only received oral calcitonin as an active treatment
Patients who only received nasal calcitonin as active treatment
Patients who did not receive any active treatment
Overall Number of Participants Analyzed 188 140 81
Least Squares Mean (Standard Deviation)
Unit of Measure: Percentage change from baseline
-29.92  (47.53) -11.41  (40.24) -11.83  (35.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Calcitonin, Nasal Calcitonin, Placebo
Comments Same as Primary Outcome
Type of Statistical Test Non-Inferiority or Equivalence
Comments Same as Primary Outcome
Statistical Test of Hypothesis P-Value 0.0012
Comments p-value not adjusted for multiple comparisons; a priori threshold for statistical significance was set at 0.05.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -18.09
Parameter Dispersion
Type: Standard Deviation
Value: 47.53
Estimation Comments oral calcitonin vs placebo
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Oral Calcitonin Nasal Calcitonin Placebo
Hide Arm/Group Description Patients who only received oral calcitonin as an active treatment Patients who only received nasal calcitonin as active treatment Patients who did not receive any active treatment
All-Cause Mortality
Oral Calcitonin Nasal Calcitonin Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Oral Calcitonin Nasal Calcitonin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/263 (7.60%)      9/182 (4.95%)      9/104 (8.65%)    
Cardiac disorders       
Angina Pectoris *  1/263 (0.38%)  1 1/182 (0.55%)  2 0/104 (0.00%)  0
Angina unstable   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Cardiac failure congestive   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Eye disorders       
Cataract   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Gastrointestinal disorders       
abdominal pain   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Gastric Ulcer   0/263 (0.00%)  0 1/182 (0.55%)  1 0/104 (0.00%)  0
Ileus   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Hepatobiliary disorders       
Biliary colic   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Cholesystitis   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Injury, poisoning and procedural complications       
Accidental overdose   1/263 (0.38%)  1 1/182 (0.55%)  1 0/104 (0.00%)  0
Upper limb fracture   1/263 (0.38%)  1 1/182 (0.55%)  1 0/104 (0.00%)  0
Facial bone fracture   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Femur fracture   0/263 (0.00%)  0 1/182 (0.55%)  1 0/104 (0.00%)  0
Foot fracture   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Hip fracture   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Wrist fracture   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Investigations       
Arthroscopy   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Musculoskeletal chest pain   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Osteoarthritis   0/263 (0.00%)  0 1/182 (0.55%)  1 0/104 (0.00%)  0
Spinal osteoarthritis   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Nervous system disorders       
Syncope   1/263 (0.38%)  1 1/182 (0.55%)  1 0/104 (0.00%)  0
Ishaemic stroke   0/263 (0.00%)  0 1/182 (0.55%)  1 0/104 (0.00%)  0
Transient ischaemic attack   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Reproductive system and breast disorders       
Endometrial hyperplasia   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Epistaxis   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Interstitial lung disease   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Skin and subcutaneous tissue disorders       
Scar   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Surgical and medical procedures       
Hysterectomy   2/263 (0.76%)  2 0/182 (0.00%)  0 0/104 (0.00%)  0
Bunion operation   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Cataract operation   1/263 (0.38%)  2 0/182 (0.00%)  0 0/104 (0.00%)  0
cholecystectomy   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Cystocele repair   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Knee arthroplasty   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Skin lesion excision   1/263 (0.38%)  1 0/182 (0.00%)  0 0/104 (0.00%)  0
Therapeutic procedure   0/263 (0.00%)  0 0/182 (0.00%)  0 1/104 (0.96%)  1
Vaginal operation   0/263 (0.00%)  0 1/182 (0.55%)  1 0/104 (0.00%)  0
Vascular disorders       
Hypertensive crisis   2/263 (0.76%)  2 0/182 (0.00%)  0 0/104 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oral Calcitonin Nasal Calcitonin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/263 (16.73%)      146/182 (80.22%)      83/104 (79.81%)    
Gastrointestinal disorders       
abdominal pain   44/263 (16.73%)  65 29/182 (15.93%)  51 15/104 (14.42%)  23
abdominal pain upper   29/263 (11.03%)  39 18/182 (9.89%)  28 9/104 (8.65%)  13
nausea   32/263 (12.17%)  40 15/182 (8.24%)  18 7/104 (6.73%)  11
constipation   18/263 (6.84%)  20 12/182 (6.59%)  14 7/104 (6.73%)  8
dyspepsia   19/263 (7.22%)  24 8/182 (4.40%)  8 3/104 (2.88%)  3
Diarrhea   17/263 (6.46%)  22 4/182 (2.20%)  5 7/104 (6.73%)  8
Infections and infestations       
Nasopharyngitis   16/263 (6.08%)  17 16/182 (8.79%)  16 10/104 (9.62%)  11
Urinary tract Infection   15/263 (5.70%)  18 17/182 (9.34%)  21 4/104 (3.85%)  6
Upper respiratory tract infection   11/263 (4.18%)  12 13/182 (7.14%)  13 8/104 (7.69%)  8
Influenza   17/263 (6.46%)  17 5/182 (2.75%)  5 2/104 (1.92%)  2
Rhinitis   6/263 (2.28%)  7 6/182 (3.30%)  12 6/104 (5.77%)  6
Musculoskeletal and connective tissue disorders       
Back pain   12/263 (4.56%)  14 13/182 (7.14%)  15 3/104 (2.88%)  6
Nervous system disorders       
Headache   20/263 (7.60%)  25 11/182 (6.04%)  13 7/104 (6.73%)  7
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. David Krause, Chief Medical Officer
Organization: Tarsa Theapeutics, Inc.
Phone: 1-267-273-7940
EMail: dkrause@tarsatherapeutics.com
Layout table for additonal information
Responsible Party: Tarsa Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00959764     History of Changes
Other Study ID Numbers: UGL-OR0801
2008-003322-42 ( EudraCT Number )
First Submitted: August 14, 2009
First Posted: August 17, 2009
Results First Submitted: October 26, 2012
Results First Posted: November 19, 2013
Last Update Posted: November 19, 2013