A Study of Oral Calcitonin Given at Night to Healthy Postmenopausal Women

Study Overview
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Brief Summary
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This study is being conducted to assess the plasma CTx-1 concentrations when dosing is at night and to compare these results with those obtained with a placebo control and with commercially available nasal calcitonin.

Detailed Description
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Timing of the dose of recombinant salmon calcitonin (rsCT) is important in effecting reduction of osteoclast activity. It is theorized that a dose administered before bedtime will be more effective than a dose administered in the morning. See protocol summary for information.

Official Title
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A Randomized, Open-Label, Placebo-Controlled, Two-Period Crossover Study of the Effect on CTx-1 Concentrations of a Single 200 μg Recombinant Salmon Calcitonin (rsCT) Dose Given at Night to Normal, Healthy, Postmenopausal Women

Conditions
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Phase 1 Pharmacodynamic Study

Intervention / Treatment
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* Drug: Oral rsCT tablet
* Drug: Oral Placebo Tablet
* Drug: Oral rsCT tablet
* Drug: Fortical (rsCT) nasal spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Postmenopausal female, in good health (at least five years since last menses). Age greater than or equal to 45 years old and less than or equal to 70 years old Weight ± 20% of the Metropolitan Life weight table. Plasma CTx-1 greater than or equal to 0.25 ng/ml. Total calcium, phosphorus, and magnesium within normal range. Willing and able to comply with all study requirements. Willing and able to sign written informed consent. Negative urine pregnancy test at screening. Negative Screen for Hepatitis B and C, HIV and drugs of abuse. Exclusion Criteria: History of parathyroid, thyroid, pituitary or adrenal diseases. History of musculoskeletal disease. History of gastro-esophageal reflux disease (GERD) or other significant gastrointestinal disorders. History of cancer within 5 years of enrollment other than basal cell carcinoma. History of regular use of a Non-Steroidal Anti-inflammatory Drug (NSAID). History of surgery within 60 days of enrollment. History of hypersensitivity or allergies (other than seasonal allergies) within -years of enrollment including known sensitivity to the active ingredients or the excipients in the study medications. Use of concomitant medications other than acetaminophen within 7 days of enrollment or anticipated need to use such concomitant medications during the study. Use of bisphosphonates within 6 months, SERMS, estrogen or estrogen-like drugs 2 months, or calcitonin 1 month. Presence of any clinically significant illness. Unwilling or unable to comply with all study requirements. Unwilling or unable to sign written, informed consent. History of drug or alcohol abuse. Participation in any clinical study of an investigational drug within 60 days of enrollment. Plasma CTx-1 less than 0.25 ng/mL.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Double Blind Oral rsCT Tablet<br>Intervention: Oral rsCT tablet given once 4 hours after evening meal. | Drug: Oral rsCT tablet<br>* On Study Day 1, subjects will be given their assigned treatment, based on one of two randomly ordered treatment sequences, at 10 PM (22:00). On Visit 3, subjects will return for administration of the second treatment with a minimum of 7 days washout interval between study drug administrations. On Visit 4, subjects will return for administration of third treatment of rsCT, either oral rsCT tablets or Fortical (rsCT) nasal spray. Interventions are described in Intervention Name, Other Names and in Intervention Description.<br>* Other names: rsCT;|
| Placebo Comparator: Part 1, Double-blind Oral Placebo Tablet<br>Intervention: Oral placebo tablet matching the oral rsCT tablet, given once 4 hours after evening meal | Drug: Oral Placebo Tablet<br>* Part 1, Double blind oral placebo tablet given once 4 hours after evening meal.<br>* Other names: Placebo;|
| Experimental: Part 2 Open label, Oral rsCT tablet<br>Intervention: Oral rsCT tablet given once 2 hours after evening meal. | Drug: Oral rsCT tablet<br>* Part 2, Open-label, oral rsCT tablet given once 2 hours after the evening meal.<br>|
| Active Comparator: Part 2, Open Label Fortical Nasal Spray<br>Intervention: Part 2 Open label. Fortical (rsCT) nasal spray given once 2 hours after evening meal | Drug: Fortical (rsCT) nasal spray<br>* Intervention: Open label, Fortical nasal spray given once 2 hours after the evening meal.<br>* Other names: Fortical nasal spray;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic Effect of Oral Calcitonin | C-terminal telopeptide of Collagen Type I (CTx-1) is an established plasma biomarker employed as an index of bone-resorption activity in response to interventions such as an anti-resorptive agent such as calcitonin. Here the calcitonin-salmon is rsCT, (recombinant) both oral and intranasal. These CTx-1 plasma concentrations were collected over 12 hours post-dosing where each subject served as her own control, as all received placebo in this crossover study, to account for the known diurnal variation of plasma CTx-1. For each time point, the ratio of the calcitonin response over the placebo response for that subject was derived from the plasma levels of CTx-1 and reported as a % of the placebo response (% Placebo or %P). These values were used to determine the primary pharmacodynamic parameter of Rmin, the minimum value seen following each active dose. The same %P values were used to derive the secondary pharmacodynamic parameters described in Secondary outc | 12 hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Derived Pharmacodynamic Parameters Further Characterizing the Effects of Oral or Intranasal Calcitonin on Plasma CTx-1, Given at Night to Post-menopausal Women | See Primary Outcome description. These CTx-1 plasma concentrations were collected over 12 hours, the values seen following active were compared with the time-matched individual values following placebo and used to derive the pharmacodynamic parameters. The primary was Rmin, seen above, and the Secondary ones were the time to that Rmin (Tmin) and the total time from the beginning of the inhibition to the end of the effect or the end of the study period (Tinhibition). | 12 hours | 
| AUCInhibition=Hours*%P | The AUCinhibition, (Area Under the Inhibition Curve) in hours*%inhibition vs placebo under the baseline line over the curve. | 12 Hours |