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

Phase 2

Completed

Interventions: Drug: Oral rsCT tablet
Drug: Oral Placebo Tablet
Drug: Fortical (rsCT) nasal spray

Brief Summary: 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: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

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.

Arm && Interventions

Group	Intervention	Description
Part 1 Double Blind Oral rsCT Tablet	Oral rsCT tablet	Intervention: Oral rsCT tablet given once 4 hours after evening meal.
Part 1, Double-blind Oral Placebo Tablet	Oral Placebo Tablet	Intervention: Oral placebo tablet matching the oral rsCT tablet, given once 4 hours after evening meal
Part 2 Open label, Oral rsCT tablet	Oral rsCT tablet	Intervention: Oral rsCT tablet given once 2 hours after evening meal.
Part 2, Open Label Fortical Nasal Spray	Fortical (rsCT) nasal spray	Intervention: Part 2 Open label. Fortical (rsCT) nasal spray given once 2 hours after evening meal

Primary Outcome Measures

Name	Time	Method
Pharmacodynamic Effect of Oral Calcitonin	12 hr	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

Secondary Outcome Measures

Name	Time	Method
Derived Pharmacodynamic Parameters Further Characterizing the Effects of Oral or Intranasal Calcitonin on Plasma CTx-1, Given at Night to Post-menopausal Women	12 hours	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).
AUCInhibition=Hours*%P	12 Hours	The AUCinhibition, (Area Under the Inhibition Curve) in hours\*%inhibition vs placebo under the baseline line over the curve.