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

NCT ID: NCT00959764

Last Updated: 2013-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 565 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2011-02-28

Brief Summary

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.

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.

Conditions

Osteoporosis, Postmenopausal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oral calcitonin and placebo nasal spray

Intervention: Oral calcitonin tablet (along with placebo intranasal spray)

Group Type: EXPERIMENTAL

Oral Calcitonin Tablets

Intervention Type: DRUG

Oral Calcitonin tablets along with matching placebo intranasal spray

Intranasal calcitonin & oral placebo

Intervention: Commercially available, active comparator, intranasal calcitonin-salmon (plus matching oral placebo tablet).

Group Type: ACTIVE_COMPARATOR

Intranasal Calcitonin

Intervention Type: DRUG

Intranasal Calcitonin Spray

Placebo: tablet & intranasal spray

Intervention: Both oral matching placebo tablets and matching intranasal placebo spray

Group Type: PLACEBO_COMPARATOR

Placebo tablets and placebo intranasal spray

Intervention Type: DRUG

Oral Placebo Tablets/Intranasal placebo spray

Interventions

Oral Calcitonin Tablets

Oral Calcitonin tablets along with matching placebo intranasal spray

Intervention Type: DRUG

Intranasal Calcitonin

Intranasal Calcitonin Spray

Intervention Type: DRUG

Placebo tablets and placebo intranasal spray

Oral Placebo Tablets/Intranasal placebo spray

Intervention Type: DRUG

Other Intervention Names

rsCT tablets; Miacalcin and Miacalcic; Matching placebos

Eligibility 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.

• Minimum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Tarsa Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Krause, M.D.

Role: STUDY_DIRECTOR

Tarsa Therapeutics, Inc.

Locations

Rheumatology Associates of N. AL, P.C.

Huntsville, Alabama, United States

Northern California Institute for Bone Health, Inc.

Oakland, California, United States

Desert Medical Advances

Palm Desert, California, United States

Bethesda Health Research Center/Bone Health Center of Bethesda

Bethesda, Maryland, United States

801 N. 30th Street, Suite 6718

Omaha, Nebraska, United States

New Mexico Clinical Research & Osteoporosis

Albuquerque, New Mexico, United States

Bone Mineral Research Center

Mineola, New York, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

University of Wisconsin-Geriatrics & Endocrinology/Medical Sciences Center

Madison, Wisconsin, United States

Diagnostic Consultative Centre, "Sveta Anna" EOOD Sofia (Rheumatology Outpatient Office)

Sofia, Sofia, Bulgaria

Synexus Hungary Ltd

Budapest, , Hungary

Synexus SCM Sp zoo

Wroclaw, Wroclaw, Poland

Clinical Research Centres SA (Pty) Ltd

Gauteng, Pretoria, South Africa

Synexus Thames Valley Clinical Research Centre

Reading, Berkshire, United Kingdom

Synexus Midlands Clinical Research Centre

Edgbaston, Birmingham, United Kingdom

Synexus Wales Clinical Research Centre

Llanishen, Cardiff, United Kingdom

Synexus Lancashire Clinical Research Centre

Chorley, Chorley, United Kingdom

Synexus Scotland Clinical Research Centre

Clydebank, Glasgow, United Kingdom

Synexus Merseyside Clinical Research Centre

Waterloo, Liverpool, United Kingdom

Synexus Manchester Clinical Research Centre

Manchester, Manchester, United Kingdom

Countries

United States; Bulgaria; Hungary; Poland; South Africa; United Kingdom

References

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.

Reference Type: RESULT

PMID: 22437792 (View on PubMed)

Other Identifiers

2008-003322-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UGL-OR0801

Identifier Type: -

Identifier Source: org_study_id