A Open-label Study Investigating the Safety and Tolerability of NPSP558, a Recombinant Human Parathyroid Hormone (rhPTH [1-84]), for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study (RACE)

• ClinicalTrials.gov Identifier: NCT01297309
• Recruitment Status: Completed
• First Posted: February 16, 2011
• Results First Posted: August 6, 2019
• Last Update Posted: May 25, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hypoparathyroidism
• Intervention: Drug: NPSP558
• Enrollment: 51

Participant Flow

Recruitment Details	The study was conducted at 12 study centers in the United States between 06 April 2011 (first participant first visit) and 08 June 2018 (last participant last visit).
Pre-assignment Details	A total of 51 participants were enrolled and 49 participants received treatment out of them 37 participants completed the study.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Period Title: Overall Study
Started	51
Treated	49
Started Extension Period	46
Completed	37
Not Completed	14
Reason Not Completed
Eligibility failure	2
Screen failure	2
Withdrawal by Subject	5
Adverse Event	1
Investigator Decision	2
Death	1
Participant not entering extensionperiod	1

Baseline Characteristics

Arm/Group Title		rhPTH (1-84)
Arm/Group Description		Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Baseline Participants		49
Baseline Analysis Population Description		Safety population included all enrolled participants who received at least 1 dose of study drug and had post baseline safety data.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	49 participants
		48.1 (9.78)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	49 participants
	Female	40 81.6%
	Male	9 18.4%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	49 participants
	Hispanic or Latino	1 2.0%
	Not Hispanic or Latino	48 98.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	49 participants
	American Indian or Alaska Native	0 0.0%
	Asian	2 4.1%
	Native Hawaiian or Other Pacific Islander	1 2.0%
	Black or African American	0 0.0%
	White	46 93.9%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE)
Description	SAE is an adverse event (AE) that results in death, life threatening, persistent or significant incapacity or substantial disruption of ability to conduct normal life functions, hospitalization or prolongation of existing hospitalization, congenital anomaly or birth defect, important medical events that may not result in death, be life threatening, or require hospitalization. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical or medicinal product. Treatment emergent adverse events (TEAEs) were defined as AEs whose onset occurs, severity worsens or intensity increases after receiving the study medication of this study and <= 30 days after last dose of study drug.
Time Frame	From start of study drug administration up to follow-up (82 months)

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least 1 dose of study drug and had post baseline safety data.

Arm/Group Title	rhPTH (1-84)
Arm/Group Description:	Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed	49
Measure Type: Count of Participants; Unit of Measure: Participants
Number of participants with TESAE	13 26.5%
Number of participants with TEAE	48 98.0%

2. Primary Outcome

Title	Number of Responders With Calcium Source at Week 52
Description	A responder was defined as a participant who met all of the following 3 criteria at each (1) a greater than (>) 50% reduction from baseline or less than (<) 500 milligram (mg) of daily calcium supplementation. (2) a >50% reduction from baseline or <0.25 microgram (mcg) of daily calcitriol supplementation. (3) an albumin-corrected total serum calcium concentration that was normalized or maintained compared to the baseline greater than or equal to (>=) 1.875 millimoles per liter (mmol/L) and not exceeding the Upper Limit of Normal (ULN) values (2.15 to 2.55 mmol/L). End of Treatment (EOT) was defined as the last determination of response or last available measurement during the treatment period. Number of responders with calcium source for citrate and carbonate at week 52 was reported here.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Arm/Group Title		rhPTH (1-84)
Arm/Group Description:		Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed		47
Measure Type: Count of Participants; Unit of Measure: Participants
Citrate (Responder)	Number Analyzed	9 participants
		7 77.8%
Carbonate (Responder)	Number Analyzed	28 participants
		21 75.0%

3. Primary Outcome

Title	Number of Responders With Calcium Source at End Of Treatment (EOT) (Up to 82 Months)
Description	A responder was defined as a participant who met all of the following 3 criteria at each (1) a greater than (>) 50% reduction from baseline or less than (<) 500 milligram (mg) of daily calcium supplementation. (2) a >50% reduction from baseline or <0.25 microgram (mcg) of daily calcitriol supplementation. (3) an albumin-corrected total serum calcium concentration that was normalized or maintained compared to the baseline greater than or equal to (>=) 1.875 millimoles per liter (mmol/L) and not exceeding the Upper Limit of Normal (ULN) values (2.15 to 2.55 mmol/L). End of Treatment (EOT) was defined as the last determination of response or last available measurement during the treatment period. Number of responders with calcium source for citrate and carbonate at EOT was reported here.
Time Frame	EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Arm/Group Title		rhPTH (1-84)
Arm/Group Description:		Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed		47
Measure Type: Count of Participants; Unit of Measure: Participants
Citrate (Responder)	Number Analyzed	11 participants
		7 63.6%
Carbonate (Responder)	Number Analyzed	29 participants
		20 69.0%

4. Secondary Outcome

Title	Percent Change From Baseline in Oral Calcium Supplementation at Week 52 and EOT (Up to 82 Months)
Description	Percent change from baseline of oral calcium supplementation were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, Week 52 and EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

Arm/Group Title	rhPTH (1-84)
Arm/Group Description:	Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed	49
Mean (Standard Deviation); Unit of Measure: % change of oral calcium supplementation
Percent change from baseline at Week 52	-68.7 (34.07)
Percent change from baseline at EOT	-39.4 (107.23)

5. Secondary Outcome

Title	Percent Change From Baseline in Oral Calcitriol Supplementation at Week 52 and EOT (Up to 82 Months)
Description	Percent change from baseline of oral calcitriol supplementation were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, Week 52 and EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

Arm/Group Title	rhPTH (1-84)
Arm/Group Description:	Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed	49
Mean (Standard Deviation); Unit of Measure: %changeoforal calcitriol supplementation
Percent change from baseline at Week 52	-72.024 (44.6232)
Percent change from baseline at EOT	-73.737 (39.3461)

6. Secondary Outcome

Title	Percent Change From Baseline in Albumin Corrected Total Serum Calcium (ACSC) at EOT (Up to 82 Months)
Description	Percent change in ACSC was reported. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

Arm/Group Title	rhPTH (1-84)
Arm/Group Description:	Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed	49
Mean (Standard Deviation); Unit of Measure: Percent change in ACSC
	-0.03 (0.190)

7. Secondary Outcome

Title	Change From Baseline in 24-Hour Urine Calcium Excretion Through EOT (Up to 82 Months)
Description	Change in 24 hour urine calcium excretion was reported. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

Arm/Group Title	rhPTH (1-84)
Arm/Group Description:	Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed	49
Mean (Standard Deviation); Unit of Measure: Millimoles per day (mmol/day)
Baseline	8.92 (5.009)
Change from Baseline at EOT	-2.37 (5.809)

8. Secondary Outcome

Title	Change From Baseline in 24-hour Urine Calcium Excretion in Participants Who Used Calcium-Sparing Diuretics Through EOT (Up to 82 Months)
Description	Change from baseline in urinary calcium concentration in participants who used at least one calcium-sparing diuretics and participants who not used calcium-sparing diuretics were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Arm/Group Title		rhPTH (1-84)
Arm/Group Description:		Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed		47
Mean (Standard Deviation); Unit of Measure: Millimoles per day (mmol/day)
EOT: Participants used calcium sparing diuretics	Number Analyzed	12 participants
		-4.07 (6.000)
EOT:Participants without calcium sparing diuretics	Number Analyzed	35 participants
		-1.79 (5.713)

9. Secondary Outcome

Title	Change From Baseline in Serum Calcium Concentration in Participants Who Used and Calcium Sparing Diuretics at EOT (Upto 82 Months)
Description	Change in serum calcium concentration of the number of participants who used at least one calcium-sparing diuretics and not used calcium sparing diuretics were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, EOT (upto 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Arm/Group Title		rhPTH (1-84)
Arm/Group Description:		Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed		49
Mean (Standard Deviation); Unit of Measure: Millimoles per liter (mmol/L)
EOT: Participants used calcium sparing diuretics	Number Analyzed	12 participants
		-0.21 (0.194)
EOT:Participants without calcium sparing diuretics	Number Analyzed	37 participants
		-0.04 (0.200)

10. Secondary Outcome

Title	Change From Baseline in Serum Phosphate at Month 72 and EOT (Upto 82 Months)
Description	Change of serum phosphate from baseline were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, Month 72, EOT (upto 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Arm/Group Title		rhPTH (1-84)
Arm/Group Description:		Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed		49
Mean (Standard Deviation); Unit of Measure: Millimoles per day (mmol/day)
Change from Baseline at Month 72	Number Analyzed	33 participants
		-0.309 (0.2280)
Change from Baseline at EOT	Number Analyzed	49 participants
		-0.254 (0.2924)

11. Secondary Outcome

Title	Number of Participants Who Maintained a Calcium Phosphate Product in A Normal Range at EOT (Up to 82 Months)
Description	The normal range of calcium phosphate product is defined as <= 4.441 millimoles square per liter square (mmol^2/L^2).
Time Frame	EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

Arm/Group Title	rhPTH (1-84)
Arm/Group Description:	Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed	49
Measure Type: Number; Unit of Measure: Count of participants
	49

12. Secondary Outcome

Title	Change From Baseline in Bone Turnover Markers at EOT (Up to 82 Months)
Description	Bone Turnover Markers such as bone specific alkaline phosphatase (BSAP), serum procollagen type 1 amino-terminal propeptide (P1NP) , osteocalcin were reported in particpiants. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Arm/Group Title		rhPTH (1-84)
Arm/Group Description:		Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed		49
Mean (Standard Deviation); Unit of Measure: Microgram per liter (μg/L)
EOT: Bone Specific alkaline phosphatase	Number Analyzed	47 participants
		5.27 (11.156)
EOT: P1NP	Number Analyzed	48 participants
		91.85 (104.327)
EOT: Osteocalcin	Number Analyzed	47 participants
		10.06 (11.570)

13. Secondary Outcome

Title	Change From Baseline in Serum Carboxy Terminal Telopeptide of Type I Collagen (s-CTx) Bone Turnover Marker at EOT (Up to 82 Months)
Description	Change form baseline in bone turnover marker (s-CTx)was reported. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Arm/Group Title	rhPTH (1-84)
Arm/Group Description:	Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed	47
Mean (Standard Deviation); Unit of Measure: Nanogram per liter (ng/L)
	224.21 (295.858)

14. Secondary Outcome

Title	Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months)
Description	Change from baseline in BMD of lumbar spine (L1-L4), hip-total, hip-trochanter, hip-intertrochanter, hip-ward's triangle, hip-femoral neck, distal one third radius at Week 52 then every 12 months until EOT were assessed by dual-energy X-ray absorptiometry [DXA] and Z-score. EOT was defined as the last determination of response or last available measurement during the treatment period.
Time Frame	Baseline, Week 52 and EOT (up to 82 months)

Outcome Measure Data

Analysis Population Description

ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Arm/Group Title		rhPTH (1-84)
Arm/Group Description:		Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Number of Participants Analyzed		49
Mean (Standard Deviation); Unit of Measure: gram per square centimeter (g/cm^2)
Lumbar Spine (L1-L4) - Change at Week 52	Number Analyzed	41 participants
		-0.0156 (0.0891)
Lumbar spine (L1-L4) - Change at EOT	Number Analyzed	44 participants
		-0.0272 (0.1111)
Hip - Total - Change at Week 52	Number Analyzed	40 participants
		-0.0189 (0.0572)
Hip - Total - Change at EOT	Number Analyzed	43 participants
		-0.0329 (0.0747)
Hip - Femoral Neck - Change at Week 52	Number Analyzed	40 participants
		-0.0278 (0.0553)
Hip - Femoral Neck - Change at EOT	Number Analyzed	43 participants
		-0.0364 (0.0848)
Hip - Trochanter - Change at Week 52	Number Analyzed	40 participants
		-0.0235 (0.0542)
Hip - Trochanter- Change at EOT	Number Analyzed	43 participants
		-0.0236 (0.1018)
Hip - Ward's Triangle - Change at Week 52	Number Analyzed	40 participants
		-0.0081 (0.0827)
Hip - Ward's Triangle - Change at EOT	Number Analyzed	43 participants
		-0.0178 (0.1014)
Distal One Third Radius - Change at Week 52	Number Analyzed	41 participants
		-0.0006 (0.0629)
Distal One Third Radius - Change at EOT	Number Analyzed	44 participants
		-0.0368 (0.0895)

Adverse Events

Time Frame	From start of study drug administration up to follow-up (Up to 82 months)
Adverse Event Reporting Description	Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
All-Cause Mortality
	rhPTH(1-84)
	Affected / at Risk (%)
Total	2/49 (4.08%)
Serious Adverse Events
	rhPTH(1-84)
	Affected / at Risk (%)	# Events
Total	13/49 (26.53%)
Cardiac disorders
Cardiac arrest * 1	1/49 (2.04%)	1
Cardiac failure congestive * 1	1/49 (2.04%)	1
Gastrointestinal disorders
Abdominal pain * 1	1/49 (2.04%)	1
General disorders
Chest discomfort * 1	1/49 (2.04%)	1
Hepatobiliary disorders
Cholecystitis * 1	1/49 (2.04%)	1
Cholelithiasis * 1	1/49 (2.04%)	2
Infections and infestations
Bronchitis viral * 1	1/49 (2.04%)	1
Cellulitis * 1	1/49 (2.04%)	1
Gastroenteritis * 1	1/49 (2.04%)	1
Groin abscess * 1	1/49 (2.04%)	1
Sepsis * 1	1/49 (2.04%)	1
Septic shock * 1	1/49 (2.04%)	1
Subcutaneous abscess * 1	1/49 (2.04%)	1
Viral infection * 1	1/49 (2.04%)	1
Injury, poisoning and procedural complications
Radius fracture * 1	1/49 (2.04%)	1
Ulna fracture * 1	1/49 (2.04%)	1
Metabolism and nutrition disorders
Hypocalcaemia * 1	1/49 (2.04%)	1
Musculoskeletal and connective tissue disorders
Back pain * 1	1/49 (2.04%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Biliary adenoma * 1	1/49 (2.04%)	2
Lung adenocarcinoma metastatic * 1	1/49 (2.04%)	1
Rectal cancer * 1	1/49 (2.04%)	1
Uterine leiomyoma * 1	1/49 (2.04%)	1
Nervous system disorders
Syncope * 1	1/49 (2.04%)	1
Renal and urinary disorders
Calculus ureteric * 1	1/49 (2.04%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	1/49 (2.04%)	1
Respiratory acidosis * 1	1/49 (2.04%)	1
Throat tightness * 1	1/49 (2.04%)	1
Skin and subcutaneous tissue disorders
Urticaria * 1	1/49 (2.04%)	1
1 Term from vocabulary, MedDRA 13.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	rhPTH(1-84)
	Affected / at Risk (%)	# Events
Total	48/49 (97.96%)
Blood and lymphatic system disorders
Anaemia * 1	3/49 (6.12%)	3
Lymphadenopathy * 1	3/49 (6.12%)	3
Cardiac disorders
Palpitations * 1	5/49 (10.20%)	5
Ear and labyrinth disorders
Vertigo * 1	3/49 (6.12%)	3
Gastrointestinal disorders
Abdominal discomfort * 1	4/49 (8.16%)	4
Abdominal pain * 1	4/49 (8.16%)	4
Colonic polyp * 1	3/49 (6.12%)	3
Constipation * 1	10/49 (20.41%)	11
Diarrhoea * 1	10/49 (20.41%)	11
Dyspepsia * 1	5/49 (10.20%)	7
Nausea * 1	15/49 (30.61%)	20
Paraesthesia oral * 1	3/49 (6.12%)	5
Toothache * 1	3/49 (6.12%)	3
Vomiting * 1	6/49 (12.24%)	6
General disorders
Chest discomfort * 1	5/49 (10.20%)	5
Fatigue * 1	8/49 (16.33%)	13
Immune system disorders
Seasonal allergy * 1	3/49 (6.12%)	3
Infections and infestations
Bronchitis * 1	12/49 (24.49%)	16
Cystitis * 1	3/49 (6.12%)	3
Ear infection * 1	5/49 (10.20%)	5
Gastroenteritis viral * 1	8/49 (16.33%)	12
Herpes zoster * 1	3/49 (6.12%)	3
Influenza * 1	10/49 (20.41%)	11
Nasopharyngitis * 1	11/49 (22.45%)	22
Sinusitis * 1	16/49 (32.65%)	31
Tooth infection * 1	4/49 (8.16%)	5
Upper respiratory tract infection * 1	8/49 (16.33%)	11
Urinary tract infection * 1	10/49 (20.41%)	14
Injury, poisoning and procedural complications
Ankle fracture * 1	3/49 (6.12%)	3
Joint sprain * 1	7/49 (14.29%)	7
Meniscus lesion * 1	3/49 (6.12%)	3
Muscle strain * 1	6/49 (12.24%)	6
Procedural pain * 1	3/49 (6.12%)	3
Investigations
Blood calcium decreased * 1	7/49 (14.29%)	7
Blood glucose increased * 1	3/49 (6.12%)	3
Urine calcium increased * 1	4/49 (8.16%)	9
Vitamin D decreased * 1	5/49 (10.20%)	5
Metabolism and nutrition disorders
Hypercalcaemia * 1	8/49 (16.33%)	11
Hypocalcaemia * 1	19/49 (38.78%)	50
Iron deficiency * 1	3/49 (6.12%)	3
Tetany * 1	7/49 (14.29%)	40
Vitamin D deficiency * 1	8/49 (16.33%)	8
Musculoskeletal and connective tissue disorders
Arthralgia * 1	13/49 (26.53%)	17
Arthritis * 1	4/49 (8.16%)	6
Back pain * 1	10/49 (20.41%)	15
Bursitis * 1	4/49 (8.16%)	4
Joint swelling * 1	3/49 (6.12%)	3
Muscle spasms * 1	19/49 (38.78%)	42
Musculoskeletal pain * 1	3/49 (6.12%)	5
Myalgia * 1	6/49 (12.24%)	10
Neck pain * 1	4/49 (8.16%)	4
Osteoarthritis * 1	3/49 (6.12%)	3
Pain in extremity * 1	10/49 (20.41%)	17
Rotator cuff syndrome * 1	3/49 (6.12%)	3
Tendonitis * 1	4/49 (8.16%)	6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma * 1	3/49 (6.12%)	3
Nervous system disorders
Dizziness * 1	7/49 (14.29%)	8
Headache * 1	13/49 (26.53%)	22
Hypoaesthesia * 1	3/49 (6.12%)	4
Migraine * 1	4/49 (8.16%)	5
Paraesthesia * 1	15/49 (30.61%)	32
Tremor * 1	4/49 (8.16%)	5
Psychiatric disorders
Anxiety * 1	7/49 (14.29%)	7
Depression * 1	3/49 (6.12%)	3
Insomnia * 1	5/49 (10.20%)	5
Renal and urinary disorders
Hypercalciuria * 1	5/49 (10.20%)	5
Nephrolithiasis * 1	6/49 (12.24%)	9
Renal cyst * 1	3/49 (6.12%)	4
Respiratory, thoracic and mediastinal disorders
Cough * 1	4/49 (8.16%)	4
Nasal congestion * 1	3/49 (6.12%)	4
Vascular disorders
Hot flush * 1	3/49 (6.12%)	3
Hypertension * 1	6/49 (12.24%)	6
1 Term from vocabulary, MedDRA 13.0; * Indicates events were collected by non-systematic assessment

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.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.

Results Point of Contact

• Name/Title: Study Director
• Organization: Shire
• Phone: +1 866 842 5335
• EMail: ClinicalTransparency@shire.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ayodele O, Mu F, Berman R, Swallow E, Rejnmark L, Gosmanova EO, Kaul S. Lower Risk of Cardiovascular Events in Adult Patients with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study. Adv Ther. 2022 Aug;39(8):3845-3856. doi: 10.1007/s12325-022-02198-y. Epub 2022 Jun 11.

Chen KS, Gosmanova EO, Curhan GC, Ketteler M, Rubin M, Swallow E, Zhao J, Wang J, Sherry N, Krasner A, Bilezikian JP. Five-year Estimated Glomerular Filtration Rate in Patients With Hypoparathyroidism Treated With and Without rhPTH(1-84). J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3557-65. doi: 10.1210/clinem/dgaa490.

Mannstadt M, Clarke BL, Bilezikian JP, Bone H, Denham D, Levine MA, Peacock M, Rothman J, Shoback DM, Warren ML, Watts NB, Lee HM, Sherry N, Vokes TJ. Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5136-5147. doi: 10.1210/jc.2019-01010.

• Responsible Party: Takeda ( Shire )
• ClinicalTrials.gov Identifier: NCT01297309
• Other Study ID Numbers: PAR-C10-008
• First Submitted: February 11, 2011
• First Posted: February 16, 2011
• Results First Submitted: June 7, 2019
• Results First Posted: August 6, 2019
• Last Update Posted: May 25, 2021