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

August 14, 2009
September 16, 2013
June 2009
February 2011   (final data collection date for primary outcome measure)
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.
Bone Mineral Density [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00959764 on ClinicalTrials.gov Archive Site
  • 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
Bone markers [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study Comparing Oral Calcitonin to Nasal Spray Calcitonin in Postmenopausal Osteoporotic Women
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Osteoporosis, Postmenopausal
  • Drug: Oral Calcitonin Tablets
    Oral Calcitonin tablets along with matching placebo intranasal spray
    Other Name: rsCT tablets
  • Drug: Intranasal Calcitonin
    Intranasal Calcitonin Spray
    Other Name: Miacalcin and Miacalcic
  • Drug: Placebo tablets and placebo intranasal spray
    Oral Placebo Tablets/Intranasal placebo spray
    Other Name: Matching placebos
  • Experimental: Oral calcitonin and placebo nasal spray
    Intervention: Oral calcitonin tablet (along with placebo intranasal spray)
    Intervention: Drug: Oral Calcitonin Tablets
  • Active Comparator: Intranasal calcitonin & oral placebo
    Intervention: Commercially available, active comparator, intranasal calcitonin-salmon (plus matching oral placebo tablet).
    Intervention: Drug: Intranasal Calcitonin
  • Placebo Comparator: Placebo: tablet & intranasal spray
    Intervention: Both oral matching placebo tablets and matching intranasal placebo spray
    Intervention: Drug: Placebo tablets and placebo intranasal spray
Binkley N, Bolognese M, Sidorowicz-Bialynicka A, Vally T, Trout R, Miller C, Buben CE, Gilligan JP, Krause DS; Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) Investigators. A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial. J Bone Miner Res. 2012 Aug;27(8):1821-9. doi: 10.1002/jbmr.1602.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
565
February 2011
February 2011   (final data collection date for primary outcome measure)

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.
Female
45 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Bulgaria,   Hungary,   Poland,   South Africa,   United Kingdom
 
NCT00959764
UGL-OR0801, 2008-003322-42
Yes
Tarsa Therapeutics, Inc.
Tarsa Therapeutics, Inc.
Not Provided
Study Director: David Krause, M.D. Tarsa Therapeutics, Inc.
Tarsa Therapeutics, Inc.
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP