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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tarsa Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00959764
First received: August 14, 2009
Last updated: September 16, 2013
Last verified: September 2013
  Purpose

The purpose of this study is to compare the effectiveness and tolerability of two medications, calcitonin nasal spray and a tablet containing calcitonin, in postmenopausal women with osteoporosis. Osteoporosis is the term used to describe a large group of diseases, which are characterized by loss of bone density, which makes the bones weaker. Osteoporosis often occurs in postmenopausal women.

Calcitonin is a hormone found in the human body. Together with other substances, it regulates the concentration of calcium in the blood and inhibits the natural resorption of bone. Both medications in this study contain salmon calcitonin (sCT), because this form of calcitonin is more active than human calcitonin when used as a medicine.

The calcitonin Nasal Spray used in this study is registered and available to doctors in United States for the treatment of osteoporosis. The medication being tested in this study is an oral tablet form of salmon calcitonin.


Condition Intervention Phase
Osteoporosis, Postmenopausal
Drug: Oral Calcitonin Tablets
Drug: Intranasal Calcitonin
Drug: Placebo tablets and placebo intranasal spray
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Multiple Dose, Placebo-Controlled, Parallel Group, 48-Week, Study of Oral Recombinant Salmon Calcitonin (rsCT) Compared to Salmon Calcitonin (sCT) Nasal Spray in Postmenopausal Osteoporotic Women

Resource links provided by NLM:


Further study details as provided by Tarsa Therapeutics, Inc.:

Primary Outcome Measures:
  • Percent Change From Baseline in Bone Mineral Density (BMD) of Axial Lumbar Spine [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Plasma C-terminal Telopeptide of Collagen 1 (CTx-1) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Plasma CTx-1 From Baseline [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Percent change from baseline of plasma CTx-1 at end of study=48 weeks


Enrollment: 565
Study Start Date: June 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral calcitonin and placebo nasal spray
Intervention: Oral calcitonin tablet (along with placebo intranasal spray)
Drug: Oral Calcitonin Tablets
Oral Calcitonin tablets along with matching placebo intranasal spray
Other Name: rsCT tablets
Active Comparator: Intranasal calcitonin & oral placebo
Intervention: Commercially available, active comparator, intranasal calcitonin-salmon (plus matching oral placebo tablet).
Drug: Intranasal Calcitonin
Intranasal Calcitonin Spray
Other Name: Miacalcin and Miacalcic
Placebo Comparator: Placebo: tablet & intranasal spray
Intervention: Both oral matching placebo tablets and matching intranasal placebo spray
Drug: Placebo tablets and placebo intranasal spray
Oral Placebo Tablets/Intranasal placebo spray
Other Name: Matching placebos

Detailed Description:

This was a randomized, double-blind, double-dummy, multiple dose, placebo-controlled, parallel group, 48- week, Phase III study. Women age 45 and over who were postmenopausal and had a diagnosis of osteoporosis were eligible for the study and were randomly allocated to one of three treatment groups; placebo tablets, oral rsCT tablets or calcitonin nasal spray. Each patient was given a treatment kit, which contained the study medication to which she had been assigned and a placebo of the treatment to which she was not assigned, or placebo nasal and oral preparations, as well as the required dietary supplements (calcium and vitamin D tablets). The study medication and supplements were self-administered at home. It was anticipated that approximately 545 patients would participate in the study.

EFFICACY: Bone Mineral Density (BMD) was recorded at Screening, Week 24, and Week 48. CTx-1 and N-telopeptide of collagen 1 (NTx-1), biochemical markers of bone resorption and total Procollagen type 1 N-terminal propeptide (P1NP),a marker of bone formation, were assessed at Week 0, Week 24, and Week 48. SAFETY: Adverse events were assessed at the clinic at Weeks 0, 12, 24, 36 and 48, and by interim phone calls at Weeks 4, 8, 16, 20, 28, 32, 40, 44, and 52. At Screening, Week 12, and Week 48, a physical examination, including nasal exam, was performed and specimens for safety laboratory analysis (clinical chemistry, hematology, and urinalysis) were collected. Sera for immunogenicity evaluations were collected at Baseline, Week 12, and Week 48.

EFFICACY: The primary comparison of interest was the percent change from baseline to 48 weeks in axial lumbar spine (L1 to L4) corrected BMD comparing the rsCT oral tablet group and the calcitonin nasal spray group. The model included the factors of the covariate (baseline BMD), treatment group, and center. The hypothesis to be tested was performed to examine the non-inferiority of the oral tablet group to the nasal spray group with respect to the percent change in axial lumbar L1-L4 spine corrected BMD. Specifically, the null hypothesis to be tested was: [Mean(oral) - Mean(placebo)] - 0.5 x [Mean(nasal) - Mean(placebo)] < 0 The alternative hypothesis was that the above expression was > 0, which implied that the oral tablet group was non-inferior to nasal spray group. The primary analysis of interest employed the modified intent-to-treat population.

SAFETY: Adverse events were summarized descriptively. Mean vital signs and clinical laboratory test results in each treatment group were compared using a one-way analysis of variance. Additionally, shift tables were prepared for each laboratory variable.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female and age 45 or over.
  • Must have undergone the onset of spontaneous or surgical menopause. Spontaneous menopause is defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels >40 milli-international units (mIU)/milliliter (mL) or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy.
  • Diagnosis of osteoporosis on the basis of an axial lumbar spine, femoral neck or total hip BMD which is below the mean for premenopausal women by a magnitude of at least 2.5 SD or 2.0 SD, if there is a documented history of a vertebral fragility fracture.
  • Must have at least three contiguous lumbar vertebrae (L1-L4) that are evaluable by DXA for BMD that is, without fracture or significant degenerative disease, as determined by Bio-Imaging Technologies, Inc.
  • No clinically significant abnormal findings in the medical history, physical exam or nasal exam.
  • No clinically significant abnormal laboratory values at the screening assessment.

Exclusion Criteria:

  • History of severe allergic disease.
  • 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.
  • Use of any intravenous bisphosphonate in the past 24 months, or >2 doses of intravenous bisphosphonate ever.
  • Use of oral bisphosphonate before randomization, including investigational bisphosphonates, unless: 1) less than 6 months of treatment and off for 6 months, or 2) 6 to 12 months of treatment and off for 2 years, or 3) More than 12 months of treatment and off for 5 years
  • Use of denosumab, fluoride, or strontium, ever.
  • Use of parathyroid hormone analogs or other bone metabolic agents within 1 year preceding randomization.
  • Any condition or disease that may interfere with the ability to have a 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, or more than 1 lumbar vertebral fracture in L1 through L4. (More than 4 vertebral fractures in T4 through L4; 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, for example, tamoxifen, tibolone, or raloxifene within 3 months preceding randomization.
  • Use of coumadin within 4 weeks preceding randomization or heparin within 1 week preceding randomization.
  • Chronic systemic treatment with glucocorticoids, hormone replacement therapy, calcitonin or any other medication within the previous three months which, in the opinion of the Investigator, would interfere with the study.
  • 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 patient.
  • 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.
  • 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.
  • History of drug or alcohol abuse, or intake of more than 30 units of alcohol weekly.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00959764

Locations
United States, Alabama
Rheumatology Associates of N. AL, P.C.
Huntsville, Alabama, United States, 35801
United States, California
Northern California Institute for Bone Health, Inc.
Oakland, California, United States, 94609
Desert Medical Advances
Palm Desert, California, United States, 92260
United States, Maryland
Bethesda Health Research Center/Bone Health Center of Bethesda
Bethesda, Maryland, United States, 20817
United States, Nebraska
801 N. 30th Street, Suite 6718
Omaha, Nebraska, United States, 68131
United States, New Mexico
New Mexico Clinical Research & Osteoporosis
Albuquerque, New Mexico, United States, 87106
United States, New York
Bone Mineral Research Center
Mineola, New York, United States, 11501
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
United States, Wisconsin
University of Wisconsin-Geriatrics & Endocrinology/Medical Sciences Center
Madison, Wisconsin, United States, 53705
Bulgaria
Diagnostic Consultative Centre, "Sveta Anna" EOOD Sofia (Rheumatology Outpatient Office)
Sofia, Bulgaria, 1784
Hungary
Synexus Hungary Ltd
Budapest, Hungary, 1036
Poland
Synexus SCM Sp zoo
Wroclaw, Poland, 50-088
South Africa
Clinical Research Centres SA (Pty) Ltd
Gauteng, Pretoria, South Africa, 0184
United Kingdom
Synexus Thames Valley Clinical Research Centre
Reading, Berkshire, United Kingdom, RG2 7AG
Synexus Midlands Clinical Research Centre
Edgbaston, Birmingham, United Kingdom, B15 2SQ
Synexus Wales Clinical Research Centre
Llanishen, Cardiff, United Kingdom, CF14 5GJ
Synexus Scotland Clinical Research Centre
Clydebank, Glasgow, United Kingdom, G81 2DR
Synexus Merseyside Clinical Research Centre
Waterloo, Liverpool, United Kingdom, L22 0LG
Synexus Lancashire Clinical Research Centre
Chorley, United Kingdom, PR7 7NA
Synexus Manchester Clinical Research Centre
Manchester, United Kingdom, M15 6SX
Sponsors and Collaborators
Tarsa Therapeutics, Inc.
Investigators
Study Director: David Krause, M.D. Tarsa Therapeutics, Inc.
  More Information

Publications:
Responsible Party: Tarsa Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00959764     History of Changes
Other Study ID Numbers: UGL-OR0801, 2008-003322-42
Study First Received: August 14, 2009
Results First Received: October 26, 2012
Last Updated: September 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases
Bone Diseases, Metabolic
Musculoskeletal Diseases
Calcitonin
Calcitonin Gene-Related Peptide
Salmon calcitonin
Bone Density Conservation Agents
Cardiovascular Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 23, 2014