Trial Outcomes & Findings for A Study of Oral Calcitonin Given at Night to Healthy Postmenopausal Women (NCT NCT00803686)

Last Updated: 2014-06-09

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

12 hr

Results posted on

2014-06-09

Participant Flow

Participant milestones

Participant milestones
Measure	Oral Recombinant Salmon Calcitonin (rsCT) In Part 1, Period 1, 6 Subjects each were given rsCT tablets or 4 hours after the evening meal. In Part 1 Period 2, the same subjects were crossed over and given oral placebo 4 hours after the evening meal.	Oral Placebo In Part 1, Period 1, 6 Subjects each were given oral placebo tablets 4 hours after the evening meal. In Part 1 Period 2, the same subjects were crossed over and given oral rsCT tablets 4 hours after the evening meal.	Oral rsCT Tablets (Part 2, Period 3) After completing Part 1, Periods 1 and 2, subjects were re-randomized to enter open label Part 2, Period 3, and received oral rsCT tablets given 2 hours after the evening meal.	Fortical Nasal Spray (Part 2, Period 3) After completing Part 1, Periods 1 and 2, subjects were re-randomized to enter the open label Part 2, Period 3 and were given Fortical Nasal Spray 2 hours after the evening meal
Part 1, Period 1 STARTED	6	6	0	0
Part 1, Period 1 COMPLETED	6	6	0	0
Part 1, Period 1 NOT COMPLETED	0	0	0	0
Part 1, Period 2 STARTED	6	6	0	0
Part 1, Period 2 COMPLETED	6	6	0	0
Part 1, Period 2 NOT COMPLETED	0	0	0	0
Part 2, Period 3 STARTED	0	0	5	4
Part 2, Period 3 COMPLETED	0	0	5	4
Part 2, Period 3 NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 Oral rsCT Tablets n=6 Participants Subjects were given oral rsCT tablets 4 hours after the evening meal	Part 1 Oral Placebo Tablets n=6 Participants Subjects were given oral placebo tablets 4 hours after the evening meal.	Part 2 Open Label--Oral rsCT Tablets After completing Part 1, Periods 1 and 2, subjects were eligible to participate in the open label Part 2 (Period 3) when oral rsCT tablets were given 2 hours after the evening meal.	Part 2 Open Label Fortical Intranasal Spray After completing Part 1, Periods 1 and 2, subjects were eligible to participate in the open label Part 2,(Period 3) when they received Fortical intra-nasal spray 2 hours after the evening meal	Total n=12 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 4.7 • n=5 Participants	59.3 years STANDARD_DEVIATION 4.7 • n=7 Participants	—	—	59.3 years STANDARD_DEVIATION 4.7 • n=21 Participants
Gender Female	6 participants n=5 Participants	6 participants n=7 Participants	—	—	12 participants n=21 Participants
Gender Male	0 participants n=5 Participants	0 participants n=7 Participants	—	—	0 participants n=21 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	—	—	12 participants n=21 Participants
post-menopausal healthy females	6 participants n=5 Participants	6 participants n=7 Participants	—	—	12 participants n=21 Participants
post-menopausal females	6 participants n=5 Participants	6 participants n=7 Participants	—	—	12 participants n=21 Participants

PRIMARY outcome

Timeframe: 12 hr

Population: Not applicable. All participants who received treatment were included.

Outcome measures

Outcome measures
Measure	Part 1 Oral rsCT Tablets n=12 Participants In this arm, Subjects were given oral rsCT tablets 4 hours after the evening meal.	Part 1 Oral Placebo Tablets n=12 Participants In this arm, subjects were given oral placebo tablets 4 hours after the evening meal.	Part 2 Oral rsCT Tablets n=5 Participants Subjects were given oral rsCT tablets four hours after the evening meal	Part 2 Fortical Intra-nasal Spray n=4 Participants Subjects were given Fortical (rsCT) nasal spray four hours after the evening meal
Pharmacodynamic Effect of Oral Calcitonin	37.5 percentage of time-matched placebo respo Standard Deviation 13.2	100 percentage of time-matched placebo respo Standard Deviation NA As all values were converted to 100 percent, there was no variability	41.2 percentage of time-matched placebo respo Standard Deviation 16.6	44.4 percentage of time-matched placebo respo Standard Deviation 21.8

SECONDARY outcome

Timeframe: 12 hours

Population: Data from Part 1 (crossover Periods 1 and 2) were pooled to give CTx-1 mean data for the oral rsCT tablet group (n = 12) and for the oral placebo group n = 12). Part 2, open-label, non-crossover, compared the CTx-1 results after oral rsCT (n = 5) with those after Fortical(n = 4. The % inhibition is reported first.

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).

Outcome measures

Outcome measures
Measure	Part 1 Oral rsCT Tablets n=12 Participants In this arm, Subjects were given oral rsCT tablets 4 hours after the evening meal.	Part 1 Oral Placebo Tablets n=12 Participants In this arm, subjects were given oral placebo tablets 4 hours after the evening meal.	Part 2 Oral rsCT Tablets n=4 Participants Subjects were given oral rsCT tablets four hours after the evening meal	Part 2 Fortical Intra-nasal Spray n=5 Participants Subjects were given Fortical (rsCT) nasal spray four hours after the evening meal
Derived Pharmacodynamic Parameters Further Characterizing the Effects of Oral or Intranasal Calcitonin on Plasma CTx-1, Given at Night to Post-menopausal Women Tmin=time in hours to Rmin	7.5 Hours Standard Deviation 5.0	0 Hours Standard Deviation 0	4.5 Hours Standard Deviation 5.0	4.0 Hours Standard Deviation 3.5
Derived Pharmacodynamic Parameters Further Characterizing the Effects of Oral or Intranasal Calcitonin on Plasma CTx-1, Given at Night to Post-menopausal Women TInhibition=total time of effect in hours	10.9 Hours Standard Deviation 2.0	0 Hours Standard Deviation 0	9.9 Hours Standard Deviation 2.6	10.7 Hours Standard Deviation 3.0

SECONDARY outcome

Timeframe: 12 Hours

The AUCinhibition, (Area Under the Inhibition Curve) in hours\*%inhibition vs placebo under the baseline line over the curve.

Outcome measures

Outcome measures
Measure	Part 1 Oral rsCT Tablets n=12 Participants In this arm, Subjects were given oral rsCT tablets 4 hours after the evening meal.	Part 1 Oral Placebo Tablets n=12 Participants In this arm, subjects were given oral placebo tablets 4 hours after the evening meal.	Part 2 Oral rsCT Tablets n=4 Participants Subjects were given oral rsCT tablets four hours after the evening meal	Part 2 Fortical Intra-nasal Spray n=5 Participants Subjects were given Fortical (rsCT) nasal spray four hours after the evening meal
AUCInhibition=Hours*%P	474.7 hours*%P Standard Deviation 267.7	0 hours*%P Standard Deviation 0	345.8 hours*%P Standard Deviation 279.0	504.7 hours*%P Standard Deviation 477.4

Adverse Events

Part 1 Oral rsCT Tablets

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1 Oral Placebo Tablets

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 2 Open Label--Oral rsCT Tablets

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 2 Open Label Fortical Intranasal Spray

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Part 1 Oral rsCT Tablets n=12 participants at risk Subjects were given oral rsCT tablets 4 hours after the evening meal	Part 1 Oral Placebo Tablets n=12 participants at risk Subjects were given oral placebo tablets 4 hours after the evening meal.	Part 2 Open Label--Oral rsCT Tablets n=5 participants at risk After completing Part 1, Periods 1 and 2, subjects were eligible to participate in the open label Part 2 (Period 3) when oral rsCT tablets were given 2 hours after the evening meal.	Part 2 Open Label Fortical Intranasal Spray n=4 participants at risk After completing Part 1, Periods 1 and 2, subjects were eligible to participate in the open label Part 2,(Period 3) when they received Fortical intra-nasal spray 2 hours after the evening meal
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/12 • Any time within the treatment period up to 30 days after treatment	0.00% 0/12 • Any time within the treatment period up to 30 days after treatment	0.00% 0/5 • Any time within the treatment period up to 30 days after treatment	25.0% 1/4 • Number of events 1 • Any time within the treatment period up to 30 days after treatment
Nervous system disorders Headache	8.3% 1/12 • Number of events 1 • Any time within the treatment period up to 30 days after treatment	0.00% 0/12 • Any time within the treatment period up to 30 days after treatment	0.00% 0/5 • Any time within the treatment period up to 30 days after treatment	0.00% 0/4 • Any time within the treatment period up to 30 days after treatment
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/12 • Any time within the treatment period up to 30 days after treatment	8.3% 1/12 • Number of events 1 • Any time within the treatment period up to 30 days after treatment	0.00% 0/5 • Any time within the treatment period up to 30 days after treatment	0.00% 0/4 • Any time within the treatment period up to 30 days after treatment
Musculoskeletal and connective tissue disorders eyelid edema	0.00% 0/12 • Any time within the treatment period up to 30 days after treatment	8.3% 1/12 • Number of events 1 • Any time within the treatment period up to 30 days after treatment	0.00% 0/5 • Any time within the treatment period up to 30 days after treatment	0.00% 0/4 • Any time within the treatment period up to 30 days after treatment
Gastrointestinal disorders abdominal pain upper	0.00% 0/12 • Any time within the treatment period up to 30 days after treatment	8.3% 1/12 • Number of events 1 • Any time within the treatment period up to 30 days after treatment	0.00% 0/5 • Any time within the treatment period up to 30 days after treatment	0.00% 0/4 • Any time within the treatment period up to 30 days after treatment

Additional Information

Nicholas LaBella, Jr. Vice-President Global RA/QA

Tarsa Therapeutics, Inc

Phone: 267-273-7944

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Except as provided herein or as required by applicable law, you agree that you shall keep such Unigene Information confidential and that you shall not, without our prior written consent, transmit, publish, or otherwise disclose to any person or entity either (i) the Unigene Information, (ii) the fact of our disclosure of the Unigene Information to you, or (iii) the existence or terms of any negotiations or discussions between us regarding your potential engagement.
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