Adherence to PTH(1-84) Treatment (FP-002-IM)

• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Type	Observational
Study Design	Observational Model: Case-Only; Time Perspective: Prospective
Condition	Clinical Use of PTH(1-84)
Intervention	Drug: Parathyroid Hormone (PTH) (1-84)
Enrollment	1179

Participant Flow

Recruitment Details	Participants took part in the study at 120 investigative sites in Austria, Denmark, Germany, Greece, Ireland, the Netherlands, Spain, and the United Kingdom from 1 April 2007 to 6 March 2013.
Pre-assignment Details	Participants with a diagnosis of osteoporosis and prescribed parathyroid hormone (PTH)(1-84) in a normal clinical setting were enrolled in this non-interventional study for 24 months observation. 1179 participants were enrolled however for 9 patients the data was missing.

Arm/Group Title	Parathyroid Hormone (PTH) (1-84)
Arm/Group Description	PTH(1-84) was prescribed in accordance with the terms of the marketing authorization. Participants were observed for 24 months.
Period Title: Overall Study
Started	1170
Completed	761
Not Completed	409

Baseline Characteristics

Arm/Group Title		Parathyroid Hormone (PTH) (1-84)
Arm/Group Description		PTH(1-84) was prescribed in accordance with the terms of the marketing authorization. Participants were observed for 24 months.
Overall Number of Baseline Participants		1170
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1170 participants
		72.3 (9.05)
Sex/Gender, Customized [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Male		19
Female		1149
Missing		2
		[1] Measure Description: Although the indication in the Summary of Product characteristics is only females, some males were initially enrolled in countries where the PTH treatment is reimbursed.
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Caucasian		1165
Asian		1
African		1
Other		1
Missing		2
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Austria		158
Denmark		79
Germany		246
Greece		300
Ireland		29
Netherlands		65
Spain		272
United Kingdom		21
Height; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	1170 participants
		156.3 (7.98)
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	1170 participants
		63.4 (12.25)
Body Mass Index (BMI); Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	1170 participants
		25.9 (4.59)
Age at Onset of Menopause [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1170 participants
		47.9 (5.49)
		[1] Measure Description: Total number of menopausal participants at baseline was 1148.
Age at Onset of Menopause by Category [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
≤ 45 years		283
> 45 years		749
Missing		116
		[1] Measure Description: Total number of menopausal participants at baseline was 1148, respectively.
Type of Menopause [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Surgical		137
Natural		966
Other		25
Missing		20
		[1] Measure Description: Total number of menopausal participants at baseline was 1148.
Calcium and/or Vitamin D Supplement; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Yes		1046
No		122
Missing		2
Time Since Starting PTH(1-84); Mean (Standard Deviation); Unit of measure: Days
	Number Analyzed	1170 participants
		8.1 (15.52)
PTH (1-84) Dosing Frequency; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Once Daily		1162
Every Other Day		6
Missing		2
Family History of Osteoporosis; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Yes		223
No		896
Unknown		1
Missing		50
Alcohol Consumption; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Never		709
Occasionally		385
Daily		50
Missing		26
Current Smoker; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Yes		111
No		1057
Missing		2
Past Smoker; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Yes		159
No		1009
Missing		2
Glucocorticosteroid Use; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Yes		129
No		1038
Missing		3
Total Hip Bone Mineral Density (BMD) [1]; Mean (Standard Deviation); Unit of measure: G/cm^2
	Number Analyzed	1170 participants
		0.680 (0.1239)
		[1] Measure Description: Measured by dual energy X-ray absorptiometry (DXA). The total number of participants for whom baseline hip BMD data was available was 654.
Total Hip T-score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	1170 participants
		-2.46 (0.965)
		[1] Measure Description: T-score is the bone mineral density (BMD) at the site when compared to the young normal reference mean; a healthy thirty-year-old. Normal is a T-score of -1.0 or higher; Osteopenia is defined as between -1.0 and -2.5 Osteoporosis is defined as -2.5 or lower. The total number of participants for whom Baseline hip T-score data was available was 812.
Spine Bone Mineral Density (BMD) [1]; Mean (Standard Deviation); Unit of measure: G/cm^2
	Number Analyzed	1170 participants
		0.763 (0.1480)
		[1] Measure Description: The total number of participants for whom baseline spine bone mineral density data was available was 738.
Spine T-score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	1170 participants
		-3.10 (1.130)
		[1] Measure Description: The total number of participants for whom Baseline spine T-score data was available was 954.
Number of Participants With at Least One Fracture; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	1170 participants
		904
Was Patient/relative/helper instructed in PTH(1-84) (self) injection technique?; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1170 participants
Yes		1167
No		1
Missing		2

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Discontinued Before 6 Months of Treatment
Description	A participant was defined as "permanently discontinued" if treatment with PTH(1-84) was not ongoing at the 6-month time point and at any future time points afterwards.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	Parathyroid Hormone (PTH) (1-84)
Arm/Group Description:	PTH(1-84) was prescribed in accordance with the terms of the marketing authorization. Participants were observed for 24 months.
Overall Number of Participants Analyzed	1170
Measure Type: Number; Unit of Measure: participants
	181

2. Secondary Outcome

Title	Number of Participants Who Discontinued Before 3, 12, 18, and 24 Months of Treatment
Description	A participant was defined as “permanently discontinued” if treatment with PTH(1-84) was not ongoing at the 6-month time point and at any future time points afterwards. A participant was defined as “temporarily discontinued” if treatment with PTH(1-84) was not ongoing at the time point but was then ongoing at a future time point. This was the case when a participant or investigator wanted to pause the treatment for a length of time (e.g. because of an adverse event or interruption). Therefore, a participant was defined as still “ongoing” during the trial if treatment with PTH(1-84) had not been permanently or temporarily discontinued at that time point. A participant was only defined as “missing” or “unknown” if they attended the relevant visit and there was no result or “unknown” was entered as the result. Results for months 3, 12, 18 and 24 are cumulative data up until that time point.
Time Frame	From enrollment to 3, 12, 18, and 24 months

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	3 Months	12 Months	18 Months	24 Months
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	1170	1170	1170	1170
Measure Type: Number; Unit of Measure: participants
Permanently discontinued	75	198	284	525
Temporarily discontinued	6	8	2	2
Ongoing	898	847	709	375
Unknown	0	0	0	0
Missing	191	117	175	268

3. Secondary Outcome

Title	Duration of Treatment
Description	Duration of treatment was defined as the last known date that PTH(1-84) was taken minus the first date that PTH(1-84) was taken plus one. In the calculation of duration, no adjustment was made for the prescribed dose frequency or for periods of temporary discontinuation due to adverse drug reactions (ADRs) or temporary patient suspension of treatment.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Participants for whom data were available

Arm/Group Title	Parathyroid Hormone (PTH) (1-84)
Arm/Group Description:	PTH(1-84) was prescribed in accordance with the terms of the marketing authorization. Participants were observed for 24 months.
Overall Number of Participants Analyzed	1156
Mean (Full Range); Unit of Measure: months
	17.7; (0 to 35)

4. Secondary Outcome

Title	Treatment Compliance by Visit
Description	A participant was defined as compliant if the participant took the treatment as prescribed by the Physician, i.e. complied with the Physician’s advice and followed the treatment regimen prescribed. A participant whose dose frequency and treatment length were changed during treatment, e.g. in response to a raised serum calcium level, was regarded as fully compliant if the revised treatment regimen was adhered to. Data on compliance were obtained at each visit and relate to the period since the previous recorded visit.
Time Frame	From enrollment to 3, 6, 12, 18, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	3 Months	6 Months	12 Months	18 Months	24 Months
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	1170	1170	1170	1170	1170
Measure Type: Number; Unit of Measure: participants
Compliant	875	845	800	721	558
Non-compliant	105	80	95	89	93
Missing	190	245	275	360	519

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse drug reactions and abnormal laboratory findings related to the treatment.
Arm/Group Title	Parathyroid Hormone (PTH) (1-84)
Arm/Group Description	PTH(1-84) was prescribed in accordance with the terms of the marketing authorization. Participants were observed for 24 months.
All-Cause Mortality
	Parathyroid Hormone (PTH) (1-84)
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Parathyroid Hormone (PTH) (1-84)
	Affected / at Risk (%)
Total	10/1170 (0.85%)
Gastrointestinal disorders
Abdominal pain † 1	1/1170 (0.09%)
Diarrhoea † 1	1/1170 (0.09%)
Nausea † 1	1/1170 (0.09%)
General disorders
Pain † 1	1/1170 (0.09%)
Injury, poisoning and procedural complications
Fall † 1	1/1170 (0.09%)
Investigations
Blood calcium increased † 1	1/1170 (0.09%)
Weight decreased † 1	2/1170 (0.17%)
Metabolism and nutrition disorders
Hypercalcaemia † 1	4/1170 (0.34%)
Nervous system disorders
Dizziness † 1	1/1170 (0.09%)
Headache † 1	1/1170 (0.09%)
Tremor † 1	1/1170 (0.09%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	1/1170 (0.09%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 11.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Parathyroid Hormone (PTH) (1-84)
	Affected / at Risk (%)
Total	276/1170 (23.59%)
Cardiac disorders
Palpitations † 1	5/1170 (0.43%)
Tachycardia † 1	5/1170 (0.43%)
Ear and labyrinth disorders
Motion sickness † 1	3/1170 (0.26%)
Tinnitus † 1	1/1170 (0.09%)
Vertigo † 1	5/1170 (0.43%)
Endocrine disorders
Hyperparathyroidism † 1	1/1170 (0.09%)
Eye disorders
Panophthalmitis † 1	1/1170 (0.09%)
Visual impairment † 1	1/1170 (0.09%)
Gastrointestinal disorders
Abdominal discomfort † 1	3/1170 (0.26%)
Abdominal pain † 1	1/1170 (0.09%)
Abdominal pain upper † 1	4/1170 (0.34%)
Constipation † 1	4/1170 (0.34%)
Diarrhoea † 1	5/1170 (0.43%)
Dyspepsia † 1	1/1170 (0.09%)
Nausea † 1	66/1170 (5.64%)
Reflux gastritis † 1	1/1170 (0.09%)
Vomiting † 1	16/1170 (1.37%)
General disorders
Asthenia † 1	4/1170 (0.34%)
Chest discomfort † 1	1/1170 (0.09%)
Chills † 1	2/1170 (0.17%)
Discomfort † 1	1/1170 (0.09%)
Fatigue † 1	6/1170 (0.51%)
Feeling abnormal † 1	1/1170 (0.09%)
Gait disturbance † 1	1/1170 (0.09%)
Influenza like illness † 1	1/1170 (0.09%)
Injection site haematoma † 1	1/1170 (0.09%)
Injection site reaction † 1	1/1170 (0.09%)
Malaise † 1	9/1170 (0.77%)
Pain † 1	4/1170 (0.34%)
Pyrexia † 1	1/1170 (0.09%)
Infections and infestations
Influenza † 1	1/1170 (0.09%)
Nasopharyngitis † 1	1/1170 (0.09%)
Investigations
Blood alkaline phosphatase increased † 1	3/1170 (0.26%)
Blood calcium abnormal † 1	1/1170 (0.09%)
Blood pressure systolic increased † 1	1/1170 (0.09%)
Weight decreased † 1	2/1170 (0.17%)
Weight increased † 1	1/1170 (0.09%)
Metabolism and nutrition disorders
Anorexia † 1	3/1170 (0.26%)
Decreased appetite † 1	5/1170 (0.43%)
Hypercalcaemia † 1	123/1170 (10.51%)
Hypocalcaemia † 1	1/1170 (0.09%)
Hypocalcemia † 1	1/1170 (0.09%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	6/1170 (0.51%)
Arthropathy † 1	1/1170 (0.09%)
Back pain † 1	6/1170 (0.51%)
Bone pain † 1	2/1170 (0.17%)
Mobility decreased † 1	1/1170 (0.09%)
Muscle spasms † 1	6/1170 (0.51%)
Muscular weakness † 1	3/1170 (0.26%)
Musculoskeletal discomfort † 1	1/1170 (0.09%)
Musculoskeletal pain † 1	1/1170 (0.09%)
Musculoskeletal stiffness † 1	1/1170 (0.09%)
Myalgia † 1	3/1170 (0.26%)
Pain in extremity † 1	2/1170 (0.17%)
Nervous system disorders
Balance disorder † 1	1/1170 (0.09%)
Burning sensation mucosal † 1	1/1170 (0.09%)
Dizziness † 1	20/1170 (1.71%)
Dysgeusia † 1	1/1170 (0.09%)
Encephalopathy † 1	1/1170 (0.09%)
Headache † 1	27/1170 (2.31%)
Paraesthesia † 1	1/1170 (0.09%)
Transient ischaemic attack † 1	1/1170 (0.09%)
Tremor † 1	2/1170 (0.17%)
Psychiatric disorders
Depression † 1	3/1170 (0.26%)
Restlessness † 1	1/1170 (0.09%)
Sleep disorder † 1	1/1170 (0.09%)
Renal and urinary disorders
Hypercalciuria † 1	1/1170 (0.09%)
Nephrolithiasis † 1	1/1170 (0.09%)
Nocturia † 1	1/1170 (0.09%)
Pollakiuria † 1	2/1170 (0.17%)
Reproductive system and breast disorders
Pelvic pain † 1	1/1170 (0.09%)
Respiratory, thoracic and mediastinal disorders
Asphyxia † 1	1/1170 (0.09%)
Dyspnoea † 1	2/1170 (0.17%)
Skin and subcutaneous tissue disorders
Alopecia † 1	8/1170 (0.68%)
Hyperhidrosis † 1	1/1170 (0.09%)
Lipoatrophy † 1	1/1170 (0.09%)
Petechiae † 1	1/1170 (0.09%)
Pruritus † 1	2/1170 (0.17%)
Pruritus generalised † 1	1/1170 (0.09%)
Rash † 1	1/1170 (0.09%)
Rash generalised † 1	1/1170 (0.09%)
Rash papulosquamous † 1	1/1170 (0.09%)
Vascular disorders
Circulatory collapse † 1	1/1170 (0.09%)
Haematoma † 1	1/1170 (0.09%)
Hot flush † 1	4/1170 (0.34%)
Hypertension † 1	2/1170 (0.17%)
Hypertensive crisis † 1	1/1170 (0.09%)
Hypotension † 1	1/1170 (0.09%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 11.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Any study related publication will be multi-center or single-center publications. All proposed site publications and presentations will be submitted to (sponsor) NPS Pharmaceuticals for review in advance of publication.

Results Point of Contact

Name/Title: Medical Director

Organization: Takeda

Phone: 800-778-2860

EMail: clinicaltrialregistry@tpna.com

Responsible Party:	Takeda
ClinicalTrials.gov Identifier:	NCT00478569 History of Changes
Other Study ID Numbers:	FP-002-IM
First Submitted:	May 23, 2007
First Posted:	May 25, 2007
Results First Submitted:	April 29, 2014
Results First Posted:	May 28, 2014
Last Update Posted:	May 28, 2014