PEAK: Sequential Treatment of Postmenopausal Women With Primary Osteoporosis (FP-001-IM)

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00365456
• Collaborator: (none)
• Enrollment: 407
• Location: 1
• Arms: 2
• Duration (Months): 61
• Patients Per Site Per Month: 6.7

Study Details

Study Description

Brief Summary

The objective is to show superior efficacy of PTH (1-84) over risedronate in treating osteoporotic women for 12 months after having previously been treated with PTH (1-84) for 12 months followed by 12 months treatment with risedronate.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: Parathyroid Hormone (PTH); Drug: Risedronate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 407 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, International, Multi Centre, Parallel Group, Phase III b, Randomised Trial, Investigating Lumbar Spine Bone Mineral Density (BMD) Changes in Postmenopausal Women With Primary Osteoporosis Initially Treated With 12 Months of Full Length Parathyroid Hormone (PTH 1-84) Followed by 12 Months of Treatment With Risedronate Followed by Either 12 Months Treatment With PTH (1-84) or Risedronate.
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PTH (1-84)	Drug: Parathyroid Hormone (PTH); Self-administered (100 μg in a volume of 71.4 μL) daily as a subcutaneous injection in the abdomen using the Preotact pen.
Active Comparator: Risedronate	Drug: Risedronate; Orally once weekly as one 35 mg tablet.

Outcome Measures

Primary Outcome Measures

1. Change in Lumbar Spine BMD From Start of Trial Period III Until End of Trial Period III. [12 months]

   BMD was measured by Dual X-ray Absorptiometry (DXA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Women above the age of 50 years with the diagnosis of postmenopausal primary osteoporosis may be enrolled in the trial if the following inclusion/exclusion criteria apply.

All inclusion criteria must be answered "yes" for a subject to be enrolled in the trial.

1. Has the subject given informed consent according to local requirements before any trial related activities? (A trial related activity is any procedure that would not have been performed during the routine management of the subject).

2. Is the subject above 50 years old?

3. Is the subject postmenopausal (more than 5 years) - in the judgement of the investigator?

4. Does the subject have primary osteoporosis with a lumbar spine T score < -3.0 SD (at lumbar spine L1-L4, with a minimum of two evaluable vertebrae)?

5. Does the subject have a life expectancy of >3 years?

6. Is the subject able to self-inject PTH (1-84), (or to have PTH (1-84) injection by a helper)?

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Roskilde		Denmark

Sponsors and Collaborators

• Takeda

Investigators

• Study Chair: Nycomed Clinical Trial Operations, Headquaters

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00365456
• Other Study ID Numbers: FP-001-IM; 2005-000730-20; U1111-1132-3246
• First Posted: Aug 17, 2006
• Last Update Posted: Aug 20, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Takeda: Lumbar Spine Bone Mineral Density (BMD)
• Additional relevant MeSH terms: Osteoporosis; Risedronic Acid; Hormones; Parathyroid Hormone

Study Results

Participant Flow

Recruitment Details	The trial was divided into 3 consecutive open-label treatment phases of 12 months with randomisation after Trial Period II. From 407 enrolled patients in total, 2 patients were enrolled but were never exposed to trial treatment. Thus, 405 patients in total received trial treatment.
Pre-assignment Detail	Period I: total number of 405 patients were included and all received PTH(1-84) treatment for 1 year Period II: of those 405 patients, 282 continued into the 2. year and all received risedronate Period III: during the 3. year, the remaining 268 patients were randomised to either PTH(1-84) (=136 patients) or risedronate (=132 patients)

Arm/Group Title	PTH (1-84)	Risedronate
Arm/Group Description
Period Title: Trial Period I (12 Months)
STARTED	407	0
COMPLETED	282	0
NOT COMPLETED	125	0
Period Title: Trial Period I (12 Months)
STARTED	0	282
COMPLETED	0	268
NOT COMPLETED	0	14
Period Title: Trial Period I (12 Months)
STARTED	136	132
COMPLETED	118	127
NOT COMPLETED	18	5

Baseline Characteristics

Arm/Group Title	PTH(1-84) or Risedronate
Arm/Group Description	PTH(1-84) received by 405 participants in Trial Period I of those 405 participants, 282 received Risedronate in Trial Period II of those 282 participants, 268 participant remained and 136 received PTH(1-84) and 132 received Risedronate in Trial Period III
Overall Participants	405
Age, Customized (years) [Mean (Standard Deviation) ]
Trial Period I / PTH(1-84)	64.6 (7.46)
Trial Period II / Risedronate	64.2 (7.43)
Trial Period III / PTH(1-84)	63.4 (6.94)
Trial Period III / Risedronate	64.7 (7.91)
Sex/Gender, Customized (participants) [Number]
female	405 100%
Lumbar spine T-score (score) [Mean (Standard Deviation) ]
Trial Period I / PTH(1-84)	-3.61 (0.490)
Trial Period II / Risedronate	-3.62 (0.472)
Trial Period III / PTH(1-84)	-3.60 (0.427)
Trial Period III / Risedronate	-3.63 (0.518)
Prevalent vertebral fractures (participants) [Number]
Trial Period I / PTH(1-84)	105 25.9%
Trial Period II / Risedronate	71 17.5%
Trial Period III / PTH(1-84)	37 9.1%
Trial Period III / Risedronate	29 7.2%
Prevalent non-vertebral fragility fractures (participants) [Number]
Trial Period I / PTH(1-84): hip fractures	9 2.2%
Trial Period II / Risedronate: hip fractures	5 1.2%
Trial Period III / PTH(1-84): hip fractures	1 0.2%
Trial Period III / Risedronate: hip fractures	3 0.7%
Trial Period I / PTH(1-84): wrist fractures	78 19.3%
Trial Period II / Risedronate: wrist fractures	50 12.3%
Trial Period III / PTH(1-84): wrist fractures	22 5.4%
Trial Period III / Risedronate: wrist fractures	25 6.2%
Trial Period I / PTH(1-84): others	93 23%
Trial Period II / Risedronate: others	59 14.6%
Trial Period III / PTH(1-84): others	28 6.9%
Trial Period III / Risedronate: others	27 6.7%
Weight (kg) [Mean (Standard Deviation) ]
Trial Period I / PTH(1-84)	59.5 (9.39)
Trial Period II / Risedronate	59.7 (9.17)
Trial Period III / PTH(1-84)	59.6 (8.66)
Trial Period III / Risedronate	59.8 (9.57)
Height (cm) [Mean (Standard Deviation) ]
Trial Period I / PTH(1-84)	157.4 (6.40)
Trial Period II / Risedronate	157.5 (6.48)
Trial Period III / PTH(1-84)	157.6 (6.21)
Trial Period III / Risedronate	157.4 (6.86)
Serum Calcium (mmol/L) [Mean (Standard Deviation) ]
Trial Period I / PTH(1-84)	2.338 (0.1022)
Trial Period II / Risedronate	2.337 (0.0999)
Trial Period III / PTH(1-84)	2.337 (0.0961)
Trial Period III / Risedronate	2.339 (0.1041)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Trial Period I / PTH(1-84)	24.06 (3.861)
Trial Period II / Risedronate	24.11 (3.788)
Trial Period III / PTH(1-84)	24.06 (3.618)
Trial Period III / Risedronate	24.21 (3.933)

Outcome Measures

1. Primary Outcome

Title	Change in Lumbar Spine BMD From Start of Trial Period III Until End of Trial Period III.
Description	BMD was measured by Dual X-ray Absorptiometry (DXA).
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All randomized patients made the Full Analysis Set which was used for the primary and secondary analyses according to intention-to-treat principles. One participant excluded due to missing baseline data at trial period III entry, thus no data could be carried forward for this patient. Missing values imputed by Last Observation Carried Forward.

Arm/Group Title	PTH (1-84)	Risedronate
Arm/Group Description	Regimen 1 = PTH (1-84) → Risedronate → PTH (1-84)	Regimen 2 = PTH (1-84) → Risedronate → Risedronate
Measure Participants	135	132
Least Squares Mean (Standard Error) [Percentage Change]	1.002 (1.0037)	0.990 (1.0034)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PTH (1-84), Risedronate
	Comments	An analysis of covariance (ANCOVA) model was used including treatment group, stratum and pooled centre as fixed effects and log (BMD at Baseline III (month 24)) as a covariate (log-normally distributed data assumed). Least square mean change from baseline III (month 24), 95% confidence interval and p-value for the treatment effect (PTH (1-84) vs. Risedronate) was calculated. Superiority was claimed if lower limit of the interval was above 1. Results were back-transformed from the log scale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	No multiplicity correction of the significance level was performed as only one primary endpoint was planned.
	Method	ANCOVA
	Comments	Estimation allowing for unequal variance in the two treatment groups and robust estimates for the standard errors were obtained.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.012
	Confidence Interval	(2-Sided) 95%; 1.003 to 1.021
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0045
	Estimation Comments

Adverse Events

Time Frame	Over three years of the trial duration.
Adverse Event Reporting Description	The safety analysis set (SAF) was defined as all subjects enrolled in Trial Period I who received at least one dose of the IMP. At each contact between the site and the subject (visit or phone) the subject was asked if she has experienced any health problems since the last contact.
Arm/Group Title	PTH (1-84)		Risedronate
Arm/Group Description	Trial Period I SAEs and Trial Period III SAEs for subjects receiving PTH (1-84)		Trial Period II SAEs and Trial Period III SAEs for subjects receiving risedronate
All Cause Mortality
	PTH (1-84)		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PTH (1-84)		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/405 (8.1%)		32/282 (11.3%)
Cardiac disorders
Acute myocardial infarction	1/405 (0.2%)	1	0/282 (0%)	0
Arrhythmia	1/405 (0.2%)	1	0/282 (0%)	0
Atrial fibrillation	0/405 (0%)	0	2/282 (0.7%)	2
Coronary artery disease	0/405 (0%)	0	1/282 (0.4%)	1
Myocardial infarction	0/405 (0%)	0	1/282 (0.4%)	1
Ear and labyrinth disorders
Vertigo	1/405 (0.2%)	1	0/282 (0%)	0
Endocrine disorders
Goitre	1/405 (0.2%)	1	0/282 (0%)	0
Eye disorders
Cataract	1/405 (0.2%)	1	0/282 (0%)	0
Eye disorder	1/405 (0.2%)	1	0/282 (0%)	0
Retinal detachment	1/405 (0.2%)	1	0/282 (0%)	0
Retinal vein thrombosis	0/405 (0%)	0	1/282 (0.4%)	1
Gastrointestinal disorders
Constipation	1/405 (0.2%)	1	0/282 (0%)	0
Abdominal adhesions	0/405 (0%)	0	1/282 (0.4%)	1
General disorders
Condition aggravated	1/405 (0.2%)	1	2/282 (0.7%)	2
Hepatobiliary disorders
Cholelithiasis	1/405 (0.2%)	1	0/282 (0%)	0
Immune system disorders
Hypersensitivity	1/405 (0.2%)	1	0/282 (0%)	0
Infections and infestations
Diverticulitis	2/405 (0.5%)	2	0/282 (0%)	0
Pneumonia	1/405 (0.2%)	1	1/282 (0.4%)	1
Gastroenteritis	0/405 (0%)	0	1/282 (0.4%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/405 (0.2%)	1	0/282 (0%)	0
Contusion	1/405 (0.2%)	1	0/282 (0%)	0
Multiple injuries	1/405 (0.2%)	1	0/282 (0%)	0
Patella fracture	1/405 (0.2%)	1	0/282 (0%)	0
Pelvic fracture	1/405 (0.2%)	1	0/282 (0%)	0
Thoracic vertebral fracture	1/405 (0.2%)	1	0/282 (0%)	0
Ulna fracture	1/405 (0.2%)	1	0/282 (0%)	0
Upper limb fracture	1/405 (0.2%)	1	0/282 (0%)	0
Foot fracture	0/405 (0%)	0	2/282 (0.7%)	2
Impacted fracture	0/405 (0%)	0	1/282 (0.4%)	1
Lower limb fracture	0/405 (0%)	0	1/282 (0.4%)	1
Wrist fracture	0/405 (0%)	0	2/282 (0.7%)	2
Investigations
Electrocardiogram QT prolonged	1/405 (0.2%)	1	0/282 (0%)	0
Metabolism and nutrition disorders
Lactose intolerance	0/405 (0%)	0	1/282 (0.4%)	1
Musculoskeletal and connective tissue disorders
Metatarsalgia	1/405 (0.2%)	1	0/282 (0%)	0
Myalgia	1/405 (0.2%)	1	0/282 (0%)	0
Arthralgia	0/405 (0%)	0	1/282 (0.4%)	1
Foot deformity	0/405 (0%)	0	1/282 (0.4%)	1
Groin pain	0/405 (0%)	0	1/282 (0.4%)	1
Intervertebral disc protrusion	0/405 (0%)	0	1/282 (0.4%)	1
Musculoskeletal chest pain	0/405 (0%)	0	1/282 (0.4%)	1
Osteoarthritis	0/405 (0%)	0	2/282 (0.7%)	2
Pain in extremity	0/405 (0%)	0	1/282 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/405 (0.2%)	1	0/282 (0%)	0
Colon cancer	1/405 (0.2%)	1	1/282 (0.4%)	1
Essential thrombocythaemia	1/405 (0.2%)	1	0/282 (0%)	0
Gastric neoplasm	1/405 (0.2%)	1	0/282 (0%)	0
Thyroid neoplasm	1/405 (0.2%)	1	0/282 (0%)	0
Benign neoplasm of thyroid gland	0/405 (0%)	0	1/282 (0.4%)	1
Mesothelioma	0/405 (0%)	0	1/282 (0.4%)	1
Nervous system disorders
Dizziness	1/405 (0.2%)	1	0/282 (0%)	0
Paraesthesia	1/405 (0.2%)	1	0/282 (0%)	0
Syncope	1/405 (0.2%)	1	1/282 (0.4%)	1
Renal and urinary disorders
Urinary incontinence	2/405 (0.5%)	2	2/282 (0.7%)	2
Nephrotic syndrome	0/405 (0%)	0	1/282 (0.4%)	1
Reproductive system and breast disorders
Uterine polyp	0/405 (0%)	0	1/282 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/405 (0.2%)	1	1/282 (0.4%)	1
Lung disorder	1/405 (0.2%)	1	0/282 (0%)	0
Respiratory disorder	1/405 (0.2%)	1	0/282 (0%)	0
Skin and subcutaneous tissue disorders
Skin lesion	1/405 (0.2%)	1	0/282 (0%)	0
Surgical and medical procedures
Bunion operation	1/405 (0.2%)	1	0/282 (0%)	0
Medical device removal	0/405 (0%)	0	1/282 (0.4%)	1
Vascular disorders
Angiopathy	1/405 (0.2%)	1	0/282 (0%)	0
Femoral arterial stenosis	0/405 (0%)	0	1/282 (0.4%)	1
Hypertensive crisis	0/405 (0%)	0	1/282 (0.4%)	1
Intermittent claudication	0/405 (0%)	0	1/282 (0.4%)	1
Orthostatic hypotension	0/405 (0%)	0	1/282 (0.4%)	1
Peripheral arterial occlusive disease	0/405 (0%)	0	1/282 (0.4%)	2
Other (Not Including Serious) Adverse Events
	PTH (1-84)		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	365/405 (90.1%)		95/282 (33.7%)
Ear and labyrinth disorders
Vertigo	24/405 (5.9%)	26	0/282 (0%)	0
Gastrointestinal disorders
Nausea	98/405 (24.2%)	123	0/282 (0%)	0
General disorders
Asthenia	23/405 (5.7%)	24	0/282 (0%)	0
Infections and infestations
Urinary tract infection	23/405 (5.7%)	28	14/282 (5%)	16
Influenza	0/405 (0%)	0	20/282 (7.1%)	24
Metabolism and nutrition disorders
Hypercalcaemia	87/405 (21.5%)	105	17/282 (6%)	20
Musculoskeletal and connective tissue disorders
Back pain	31/405 (7.7%)	32	15/282 (5.3%)	15
Arthralgia	0/405 (0%)	0	14/282 (5%)	16
Osteoarthritis	0/405 (0%)	0	15/282 (5.3%)	16
Nervous system disorders
Headache	35/405 (8.6%)	40	0/282 (0%)	0
Renal and urinary disorders
Hypercalciuria	121/405 (29.9%)	150	0/282 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After publication of the results or 24 months after Clinical Trial Report has been finalised, whichever comes first, Nycomed acknowledge the Investigator's rights to publish results from this trial. Any such scientific paper, presentation, communication, or other information concerning the investigation described in this protocol, must be submitted to Nycomed prior to submission for publication/presentation for review. Review comments will be given within a month from receipt of the manuscript.