Trial Outcomes & Findings for PTH & Ibandronate Combination Study (PICS) (NCT NCT00683163)

Last Updated: 2013-11-05

Results Overview

After an overnight fast, serum was drawn at baseline and 1, 3, 6, 12, 15, 18 and 24 months. Samples were stored at -70C until batch assayed in a central laboratory. Serum N-propeptide of type I collagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) were measured by electrochemiluminescent immunoassay. Bone-specified alkaline phosphate (BAP) was measured by paramagnetic particle immunoassay. P1NP was the bone turnover marker upon which we based sample size calculations.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

44 participants

Primary outcome timeframe

Baseline, 3 months

Results posted on

2013-11-05

Participant Flow

Recruitment letters were sent to women in the San Francisco Bay Area. Telephone screening interviews were conducted and study visits were performed at the San Francisco UCSF's Mt. Zion Medical Center.

Approximately 33,000 recruitment letters were mailed to women in the San Francisco Bay Area. Approximately 1100 phone calls were fielded, and 226 women were interested and eligible for additional screening. Of 164 who attended screening visits, 44 were eligible and enrolled.

Participant milestones

Participant milestones
Measure	Concurrent (A) Concurrent Group (A) received 6 months of monthly oral ibandronate 150 mg plus daily parathyroid hormone (PTH) 1-84 1.4 mg, followed by 18 months of ibandronate only. Placebo injections were given months 13-15.	Sequential (B) Sequential Group (B) received 3 months of daily PTH 1-84 1.4 mg followed by 9 months of monthly oral ibandronate 150 mg in each of years 1 and 2. Placebo monthly pills were given months 1-3 and months 13-15, and placebo injections were given months 4-6.
Overall Study STARTED	22	22
Overall Study COMPLETED	22	22
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PTH & Ibandronate Combination Study (PICS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Concurrent (A) n=22 Participants Concurrent Group (A) received 6 months of monthly oral ibandronate 150 mg plus daily PTH 1-84 1.4 mg, followed by 18 months of ibandronate only. Placebo injections were given months 13-15.	Sequential (B) n=22 Participants Sequential Group (B) received 3 months of daily PTH 1-84 1.4 mg followed by 9 months of monthly oral ibandronate 150 mg in each of years 1 and 2. Placebo monthly pills were given months 1-3 and months 13-15, and placebo injections were given months 4-6.	Total n=44 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=93 Participants	18 Participants n=4 Participants	32 Participants n=27 Participants
Age, Categorical >=65 years	8 Participants n=93 Participants	4 Participants n=4 Participants	12 Participants n=27 Participants
Age Continuous	62.7 years STANDARD_DEVIATION 4.1 • n=93 Participants	61.2 years STANDARD_DEVIATION 4.1 • n=4 Participants	61.9 years STANDARD_DEVIATION 4.1 • n=27 Participants
Sex: Female, Male Female	22 Participants n=93 Participants	22 Participants n=4 Participants	44 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	22 participants n=93 Participants	22 participants n=4 Participants	44 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, 3 months

Population: Analyses were performed according to intention-to-treat principle. A sample size of 20 participants per group was estimated to provide 80% power to detect a change of 25ng/mL in PINP, assuming the SD of 40ng/mL observed previously with concurrent PTH(1-84) and daily alendronate.

Outcome measures

Outcome measures
Measure	Concurrent (A) n=22 Participants The Concurrent Group (A) received 6 months of monthly oral ibandronate 150 mg plus daily PTH 1-84 1.4 mg, followed by 18 months of ibandronate only. Placebo injections were given months 13-15.	Sequential (B) n=22 Participants The Sequential Group (B) received 3 months of daily PTH 1-84 1.4 mg, followed by 9 months of monthly oral ibandronate 150 mg in year 1 and again in year 2. Placebo monthly pills were given months 1-3 and months 13-15, and placebo injections were given months 4-6.
P1NP (ng/ml) Change From Baseline.	42 Percent change from baseline Interval 9.0 to 85.0	186 Percent change from baseline Interval 119.0 to 275.0

SECONDARY outcome

Timeframe: Baseline, 24 months.

Areal bone mineral density (aBMD) at the lumbar spine, hip, and distal one-third radius was assessed by dual-energy X-ray absorption at baseline and 6, 12, 18, and 24 months. The precision for aBMD is 1.0%. Volumetric BMD and bone geometry in trabecular and cortical compartments were assessed by quantitative computed tomography (QCT) at the spine and hip. The left hip was used for analysis. The precision for trabecular spine vBMD measurement is 1.0%. Trabecular spine vBMD was our primary BMD outcome, thus the one presented here.

Outcome measures

Outcome measures
Measure	Concurrent (A) n=22 Participants The Concurrent Group (A) received 6 months of monthly oral ibandronate 150 mg plus daily PTH 1-84 1.4 mg, followed by 18 months of ibandronate only. Placebo injections were given months 13-15.	Sequential (B) n=22 Participants The Sequential Group (B) received 3 months of daily PTH 1-84 1.4 mg, followed by 9 months of monthly oral ibandronate 150 mg in year 1 and again in year 2. Placebo monthly pills were given months 1-3 and months 13-15, and placebo injections were given months 4-6.
Change From Baseline in Trabecular Spine vBMD	12.5 Percent change from baseline Standard Deviation 11.2 • Interval 119.0 to 275.0	13.7 Percent change from baseline Standard Deviation 21.1 • Interval 138.0 to 300.0

Adverse Events

Concurrent (A)

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Sequential (B)

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Dennis Black

UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

Phone: 415-514-8159

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Concurrent (A) n=22 participants at risk Concurrent Group (A) received 6 months of monthly oral ibandronate 150 mg plus daily PTH 1-84 1.4 mg, followed by 18 months of ibandronate only. Placebo injections were given months 13-15.	Sequential (B) n=22 participants at risk Sequential Group (B) received 3 months of daily PTH 1-84 1.4 mg followed by 9 months of monthly oral ibandronate 150 mg in each of years 1 and 2. Placebo monthly pills were given months 1-3 and months 13-15, and placebo injections were given months 4-6.
Musculoskeletal and connective tissue disorders Arthralgia	18.2% 4/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	22.7% 5/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Musculoskeletal and connective tissue disorders Back Pain	4.5% 1/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	22.7% 5/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
General disorders Dizziness	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	13.6% 3/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
General disorders Fatigue	13.6% 3/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	4.5% 1/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
General disorders Headache	4.5% 1/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Musculoskeletal and connective tissue disorders Limb Pain	22.7% 5/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	27.3% 6/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
General disorders Myalgia	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	18.2% 4/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Gastrointestinal disorders Abdominal Discomfort	18.2% 4/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	4.5% 1/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Gastrointestinal disorders Esophageal Reflux	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	13.6% 3/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Gastrointestinal disorders Lower GI	22.7% 5/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	22.7% 5/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Gastrointestinal disorders Upper GI, Nausea/Vomiting	31.8% 7/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	31.8% 7/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Gastrointestinal disorders Upper GI, Other	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	13.6% 3/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Blood and lymphatic system disorders Labs of Interest, Hypercalcemia	18.2% 4/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	13.6% 3/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Blood and lymphatic system disorders Labs of Interest, Hypercalciuria	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	4.5% 1/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
General disorders Allergy	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	4.5% 1/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Renal and urinary disorders Genitourinary	4.5% 1/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	13.6% 3/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
General disorders Other	31.8% 7/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	27.3% 6/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Injury, poisoning and procedural complications Injection Site Complication	27.3% 6/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	36.4% 8/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Injury, poisoning and procedural complications Fracture	4.5% 1/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	13.6% 3/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Infections and infestations Infection, Other	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	0.00% 0/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.
Infections and infestations Infection, Upper Respiratory	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.	9.1% 2/22 • Adverse event data was collected for the duration of the study (2 years) for each participant.