A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism

Sponsor

Shire (Industry)

Overall Status

Completed

CT.gov ID

NCT02910466

Collaborator

(none)

Enrollment

Location

Arm

37.7

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Chronic hypoparathyroidism is a life-long and irreversible disease for which the chronic administration of rhPTH(1-84) is a potential treatment option. The group of participants in the AAAE0544 core study has been taking rhPTH(1-84) for the treatment of hypoparathyroidism for up to 11 years. This study is designed to extend this experience and gain knowledge about how safe and effective rhPTH(1-84) is in participants with hypoparathyroidism over a long-term duration.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hypoparathyroidism Hypoparathyroidism	Drug: rhPTH(1-84)	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 4, Open-Label, Single-Center Clinical Study of Extended Use of rhPTH(1-84) in Hypoparathyroidism

Actual Study Start Date :

Oct 27, 2016

Actual Primary Completion Date :

Dec 20, 2019

Actual Study Completion Date :

Dec 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rhPTH(1-84) Participants will receive 25, 50, 75, and 100 microgram (mcg) of rhPTH(1-84) subcutaneous injection to the thigh via a multidose pen injector device once daily for 36 months. The dose will be individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion to achieve a serum calcium level in the lower half of the normal range.	Drug: rhPTH(1-84) Participants will receive 25, 50, 75, and 100 microgram (mcg) of rhPTH(1-84) subcutaneous injection to the thigh via a multidose pen injector device once daily for 36 months. The dose will be individualized based on Albumin-corrected Serum Calcium (ACSC) and 24-hour calcium urinary excretion to achieve a serum calcium level in the lower half of the normal range.

Arm

Intervention/Treatment

Experimental: rhPTH(1-84)

Participants will receive 25, 50, 75, and 100 microgram (mcg) of rhPTH(1-84) subcutaneous injection to the thigh via a multidose pen injector device once daily for 36 months. The dose will be individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion to achieve a serum calcium level in the lower half of the normal range.

Drug: rhPTH(1-84)

Participants will receive 25, 50, 75, and 100 microgram (mcg) of rhPTH(1-84) subcutaneous injection to the thigh via a multidose pen injector device once daily for 36 months. The dose will be individualized based on Albumin-corrected Serum Calcium (ACSC) and 24-hour calcium urinary excretion to achieve a serum calcium level in the lower half of the normal range.

Outcome Measures

Primary Outcome Measures

Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 6 [Baseline (402), Month 6]
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 12 [Baseline (402), Month 12]
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 18 [Baseline (402), Month 18]
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 24 [Baseline (402), Month 24]
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 30 [Baseline (402), Month 30]
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 36 [Baseline (402), Month 36]
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at End of Treatment (EOT) (up to Month 36) [Baseline (402), EOT (up to Month 36)]
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.

Secondary Outcome Measures

Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36) [At Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)]
EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Albumin-corrected Serum Calcium (mmol/L) = Total Calcium (mmol/L) + 0.02 * (40 gram per liter [g/L] - Albumin [g/L]).
Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
The HPT-SD was a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None (0), Mild (1), Moderate (2), Severe (3), Very severe (4) and for items 10-13, it ranges from Not at all (0), somewhat (1), Very much (2). For symptom subscale score was calculated as average score of the items 1-7 and the impact subscale scores was calculated as average score of the items 10-13. The HPT-SD was only collected within the SHP634-402 study, as planned.
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
FACT-Cog assessment was a 37-item tool with each item rated on a 5-point scale ranging from 0 to 4. It included 4 subscales: perceived cognitive impairments (CogPCI) (20 items, Item 1 - 20, score range 0-80), impact of perceived cognitive impairments on quality of life (CogQOL ) (4 items, Item 34 - 37, score range 0-16), comments from others (CogOth) (4 items, Item 21 - 24, score range 0-16) and perceived cognitive ability (CogPCA) (9 items, Item 25 - 33 score range 0-36). CogPCI subscale and comments from others subscale and two others subscale ranged as following: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit) and 4 (very much). For all four subscales of the FACT-cog: higher scores reflect worse cognitive function. Baseline (402): the last available pre-dose value in SHP634-402. EOT: the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
FACIT fatigue questionnaire contains 13 fatigue-related questions. The responses to the 13 items on the FACIT fatigue questionnaire was measured on a 4-point Likert scale (0-4). Thus, the total score ranges from 0 to 52. High scores represent less fatigue and better quality of life. For 2 questions, item 7 'I have energy' and item 8 'I am able to do my usual activities', the item response from questionnaire will be used as item score and no conversion is needed. For the rest of 11 questions, item score was calculated as 4- item response. Fatigue total score was calculated as: Fatigue Total Score = [sum of (item scores)]*13/ (number of items answered). Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
The HADS was a 14-item scale that generates ordinal data. Seven of the items related to anxiety (Item 1, 3, 5, 7, 9, 11 and 13) and seven related to depression (Item 2, 4, 6, 8, 10, 12 and 14). The scale was designed to avoid reliance on aspects of conditions that are also common somatic symptoms of illness. Each item on the questionnaire was scored from 0-3, therefore, a person can score between 0 and 21 for either anxiety or depression. For each of the two sub-scores, if a participant obtain a score ranged from: 0 to 7, he is considered as "normal"; 8-10 = Borderline abnormal (borderline case) and 11-21 = Abnormal (case). Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36) [Baseline (402), At Month 12, 24, 36, and EOT (up to Month 36)]
SF-36 was a validated questionnaire that questions participants about perceived physical and mental health and function. SF-36 consisted of 8 scaled scores, which were weighted sums of the questions in their section. Each scale was directly transformed into 0-100 scale on the assumption that each question carries equal weight; A score of zero was equivalent to maximum disability and a score of 100 was equivalent to no disability. Eight sections included in SF-36 assessment: vitality (1=none of the time to 5=all of the time), physical functioning (1=yes, limited a lot to 3=no, not limited at all), bodily pain (1=very severe to 6=none), general health (1=poor to 5=excellent), physical role (1=all of the time to 5=none of the time), emotional role (1=all of the time to 5=none of the time), social role (1=all of the time: to 5=none of the time) and mental health (1=all of the time to 5=none of the time). Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
Change from baseline in concentration of bone turnover markers included; Serum carboxy-terminal 4 telopeptide of type I collagen [s-CTX], procollagen type I amino-terminal propeptide [P1NP], osteocalcin, and sclerostin. Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
Change from baseline in concentration of bone turnover markers included, bone specific alkaline phosphatase [BSAP] and tartrate-resistant acid phosphatase-5b (TRAP-5b). Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
Change from baseline in bone architecture was assessed by using DXA. The DXA scans was evaluated for BMD of the lumbar spine (vertebra L1, L2, L3, L4), total hip and femoral neck, and distal radius. Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
Change from baseline in bone architecture was assessed by using DXA. The DXA scans was evaluated for Total T-score of the lumbar spine (vertebra L1-L4), hip (total and femoral neck), and ⅓ distal radius. Baseline (402) was defined as the last available pre-dose value in SHP634-402. The T-score was a comparison of a person's bone density with that of a healthy 30-year-old adult of the same sex and ethnicity. T-score included: Normal: >= -1; Osteopenia: < -1 and > -2.5; Osteoporosis: <= -2.5. A lower T-score implies a lower bone mineral density. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36) [Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)]
Change from baseline in bone architecture was assessed by using HRpQCT. The HRpQCT analyses included both radius and tibia of total area position. Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Mean Bone Histology (Biopsy) of Adjusted Apposition Rate and Cancellous Minimum Apposition Rate at Month 12, and EOT (up to Month 36) [At Month 12, and EOT (up to Month 36)]
Bone histology parameters consisted of adjusted apposition rate and cancellous minimum apposition rate. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Mean Bone Histology (Biopsy) of Bone Formation Rate at Month 12, and EOT (up to Month 36) [At Month 12, and EOT (up to Month 36)]
Bone histology parameters consisted of bone formation rate. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, "mcm^3/mcm^2/d" is abbreviated as micro cubic meter per micro square meter per day.
Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36) [At Month 12, and EOT (up to Month 36)]
Bone histology parameters consisted of cancellous bone volume, cancellous eroded surface, cancellous mineral surface, and cancellous osteoid surface. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Mean Bone Histology (Biopsy) of Cancellous Osteoid Thickness and Cortical Width at Month 12, and EOT (up to Month 36) [At Month 12, and EOT (up to Month 36)]
Bone histology parameters consisted of cancellous osteoid thickness and cortical width. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Participants that are currently or previously enrolled in the core study (AAAE0544 [NCT01199614]) and have maintained uninterrupted therapy with recombinant human parathyroid hormone (rhPTH(1-84)) (transient interruptions of up to 1 month continuously off treatment may be allowed).
Signed and dated informed consent form (ICF).
Adult men and women 18 to 85 years of age.
History of hypoparathyroidism for at least 12 months prior to rhPTH(1-84) treatment, defined by the requirement for supplemental calcium and/or active vitamin D to maintain serum calcium along with an undetectable or insufficient Parathyroid hormone (PTH) concentration.
Able to perform daily subcutaneous (SC) self-injections of study medication (or have designee perform injection).
Willingness and ability to understand and comply with the protocol. Women must agree to pregnancy testing and acceptable methods of contraception, as detailed in the protocol.

Exclusion Criteria

The participant is treated or has been treated with any investigational drug, aside from rhPTH(1-84), within 30 days of consent.
As assessed by the investigator, the participant has any safety or medical issues that contraindicate participation in the study.
The participant and/or the participant's parent(s) or legally-authorized representative(s) are unable to understand the nature, scope, and possible consequences of the study.
The participant is unable to comply with the protocol, example, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for evaluations, or is otherwise unlikely to complete the study, as determined by the investigator or the medical monitor.
The participant is pregnant or lactating.
Participants who are at increased baseline risk for osteosarcoma such as participant with Paget's disease of bone or unexplained new elevations of alkaline phosphatase, participants with hereditary disorders predisposing to osteosarcoma or participants with a prior history of external beam or implant radiation therapy involving the skeleton.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

Shire

Investigators

Study Director: Study Director, Shire

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Shire

ClinicalTrials.gov Identifier:

NCT02910466

Other Study ID Numbers:

SHP634-402

First Posted:

Sep 22, 2016

Last Update Posted:

Jul 28, 2021

Last Verified:

Jul 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Hypoparathyroidism

Study Results

Participant Flow

Recruitment Details

The study was conducted at a single site in the United States between 27 October 2016 (first participant first visit) and 20 December 2019 (last participant last visit).

Pre-assignment Detail

A total of 39 participants were enrolled in the study who were treated in the core AAAE0544 (NCT01199614) study, out of which, 36 participants received treatment in this study. This study reports the additional data only for the current study (SHP634-402) which is on long term safety and efficacy of over 36 months of exposure to rhPTH(1-84), and the results for core study AAAE0544 (NCT01199614) will be posted separately, as planned.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Period Title: Overall Study
STARTED	39
Safety Set	39
Treated	36
COMPLETED	0
NOT COMPLETED	39

Baseline Characteristics

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Overall Participants	39
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.9 (12.22)
Sex: Female, Male (Count of Participants)
Female	31 79.5%
Male	8 20.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.6%
Not Hispanic or Latino	34 87.2%
Unknown or Not Reported	4 10.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	38 97.4%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 6
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Time Frame	Baseline (402), Month 6

Outcome Measure Data

Analysis Population Description
Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	23
Mean (Standard Deviation) [Millimole per liter (mmol/L)]	-0.005 (0.1546)

2. Primary Outcome

Title	Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 12
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Time Frame	Baseline (402), Month 12

Outcome Measure Data

Analysis Population Description
Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	29
Mean (Standard Deviation) [mmol/L]	0.069 (0.1838)

3. Primary Outcome

Title	Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 18
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Time Frame	Baseline (402), Month 18

Outcome Measure Data

Analysis Population Description
Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	30
Mean (Standard Deviation) [mmol/L]	0.066 (0.2158)

4. Primary Outcome

Title	Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 24
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Time Frame	Baseline (402), Month 24

Outcome Measure Data

Analysis Population Description
Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	27
Mean (Standard Deviation) [mmol/L]	0.112 (0.2314)

5. Primary Outcome

Title	Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 30
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Time Frame	Baseline (402), Month 30

Outcome Measure Data

Analysis Population Description
Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	21
Mean (Standard Deviation) [mmol/L]	0.145 (0.2447)

6. Primary Outcome

Title	Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 36
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Time Frame	Baseline (402), Month 36

Outcome Measure Data

Analysis Population Description
Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	1
Mean (Standard Deviation) [mmol/L]	0.170 (NA)

7. Primary Outcome

Title	Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at End of Treatment (EOT) (up to Month 36)
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	Baseline (402), EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description
Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	33
Mean (Standard Deviation) [mmol/L]	0.135 (0.2260)

8. Secondary Outcome

Title	Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
Description	EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Albumin-corrected Serum Calcium (mmol/L) = Total Calcium (mmol/L) + 0.02 * (40 gram per liter [g/L] - Albumin [g/L]).
Time Frame	At Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description
Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Analysis Population Description

Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	36
At Month 6: less than (<) 1.875 mmol/L	20.8 53.3%
At Month 6: 1.875 mmol/L to ULN	79.2 203.1%
At Month 6: >ULN	0 0%
At Month 12: <1.875 mmol/L	31.3 80.3%
At Month 12: 1.875 mmol/L to ULN	65.6 168.2%
At Month 12: > ULN	3.1 7.9%
At Month 18: <1.875 mmol/L	24.2 62.1%
At Month 18: 1.875 mmol/L to ULN	75.8 194.4%
At Month 18: >ULN	0 0%
At Month 24: <1.875 mmol/L	16.7 42.8%
At Month 24: 1.875 mmol/L to ULN	83.3 213.6%
At Month 24: >ULN	0 0%
At Month 30: <1.875 mmol/L	17.4 44.6%
At Month 30: 1.875 mmol/L to ULN	78.3 200.8%
At Month 30: >ULN	4.3 11%
At Month 36: <1.875 mmol/L	0 0%
At Month 36: 1.875 mmol/L to ULN	100 256.4%
At Month 36: >ULN	0 0%
At EOT (up to Month 36): <1.875 mmol/L	13.9 35.6%
At EOT (up to Month 36): 1.875 mmol/L to ULN	83.3 213.6%
At EOT (up to Month 36): >ULN	2.8 7.2%

9. Secondary Outcome

Title	Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description
Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	34
Change at Month 6	-0.403 (2.7785)
Change at Month 12	0.442 (2.7419)
Change at Month 18	0.946 (3.2615)
Change at Month 24	1.378 (3.1076)
Change at Month 30	2.163 (4.2794)
Change at EOT (up to Month 36)	1.213 (3.3632)

10. Secondary Outcome

Title	Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description
Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	33
Change at Month 6	0.041 (0.2282)
Change at Month 12	0.077 (0.2925)
Change at Month 18	0.070 (0.3213)
Change at Month 24	0.074 (0.2825)
Change at Month 30	0.012 (0.2992)
Change at Month 36	-0.040 (NA)
Change at EOT (up to Month 36)	0.055 (0.2861)

11. Secondary Outcome

Title	Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description
Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	36
Calcium Prescribed Data: Change at Month 6	52.1 (547.62)
Calcium Prescribed Data: Change at Month 12	-125.6 (1189.52)
Calcium Prescribed Data: Change at Month 18	-150.9 (1140.42)
Calcium Prescribed Data: Change at Month 24	-146.0 (1401.84)
Calcium Prescribed Data: Change at Month 30	-105.7 (1262.95)
Calcium Prescribed Data: Change at Month 36	230.0 (NA)
Calcium Prescribed Data: Change at EOT (up to Month 36)	-237.8 (1208.06)
Elemental Calcium Prescribed Data: Change at Month 6	-71.35 (360.730)
Elemental Calcium Prescribed Data: Change at Month 12	-201.62 (719.878)
Elemental Calcium Prescribed Data: Change at Month 18	-206.40 (727.017)
Elemental Calcium Prescribed Data: Change at Month 24	-239.71 (898.529)
Elemental Calcium Prescribed Data: Change at Month 30	-175.56 (861.198)
Elemental Calcium Prescribed Data: Change at Month 36	-267.70 (NA)
Elemental Calcium Prescribed Data: Change at EOT (up to Month 36)	-224.31 (766.956)
Calcium Diary Data: Change at Month 6	537.420 (679.5444)
Calcium Diary Data: Change at Month 12	549.757 (974.4770)
Calcium Diary Data: Change at Month 18	1241.382 (3353.7093)
Calcium Diary Data: Change at Month 24	375.005 (797.0665)
Calcium Diary Data: Change at Month 30	102.174 (240.7955)
Calcium Diary Data: Change at Month 36	0.000 (NA)
Calcium Diary Data: Change at EOT (up to Month 36)	75.545 (220.3270)
Elemental Calcium Diary Data: Change at Month 6	151.528 (197.2856)
Elemental Calcium Diary Data: Change at Month 12	194.332 (414.3470)
Elemental Calcium Diary Data: Change at Month 18	418.160 (1334.7574)
Elemental Calcium Diary Data: Change at Month 24	145.618 (348.2148)
Elemental Calcium Diary Data: Change at Month 30	28.854 (67.2635)
Elemental Calcium Diary Data: Change at Month 36	0.000 (NA)
Elemental Calcium Diary Data: Change at EOT (up to Month 36)	25.868 (80.6473)

12. Secondary Outcome

Title	Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description
Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	36
Prescribed Data: Change at Month 6	-0.012 (0.0514)
Prescribed Data: Change at Month 12	-0.056 (0.2747)
Prescribed Data: Change at Month 18	-0.062 (0.3125)
Prescribed Data: Change at Month 24	-0.092 (0.3565)
Prescribed Data: Change at Month 30	-0.034 (0.3559)
Prescribed Data: Change at Month 36	0.000 (NA)
Prescribed Data: Change at EOT (up to Month 36)	-0.063 (0.4022)
Diary Data: Change at Month 6	0.063 (0.2117)
Diary Data: Change at Month 12	0.032 (0.1109)
Diary Data: Change at Month 18	0.015 (0.0606)
Diary Data: Change at Month 24	0.092 (0.3742)
Diary Data: Change at Month 30	0.000 (0.0000)
Diary Data: Change at Month 36	0.000 (NA)
Diary Data: Change at EOT (up to Month 36)	0.000 (0.0000)

13. Secondary Outcome

Title	Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	The HPT-SD was a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None (0), Mild (1), Moderate (2), Severe (3), Very severe (4) and for items 10-13, it ranges from Not at all (0), somewhat (1), Very much (2). For symptom subscale score was calculated as average score of the items 1-7 and the impact subscale scores was calculated as average score of the items 10-13. The HPT-SD was only collected within the SHP634-402 study, as planned.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description
Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	33
Symptom Subscale: Change at Month 6	0.06 (0.680)
Symptom Subscale: Change at Month 12	-0.31 (0.762)
Symptom Subscale: Change at Month 18	-0.27 (0.831)
Symptom Subscale: Change at Month 24	-0.25 (0.544)
Symptom Subscale: Change at Month 30	-0.20 (0.737)
Symptom Subscale: Change at Month 36	0.00 (NA)
Symptom Subscale: Change at EOT (up to Month 36)	-0.15 (0.867)
Anxiety: Change at Month 6	0.1 (0.64)
Anxiety: Change at Month 12	0.1 (0.74)
Anxiety: Change at Month 18	0.0 (0.68)
Anxiety: Change at Month 24	0.1 (0.75)
Anxiety: Change at Month 30	0.2 (0.74)
Anxiety: Change at Month 36	0.0 (NA)
Anxiety: Change at EOT (up to Month 36)	0.3 (0.80)
Sadness and Depression: Change at Month 6	0.3 (0.65)
Sadness and Depression: Change at Month 12	-0.1 (0.58)
Sadness and Depression: Change at Month 18	0.0 (0.66)
Sadness and Depression: Change at Month 24	0.3 (0.72)
Sadness and Depression: Change at Month 30	0.2 (0.95)
Sadness and Depression: Change at Month 36	0.0 (NA)
Sadness and Depression: Change at EOT (up to Month 36)	0.2 (0.95)
Impact Subscale: Change at Month 6	-0.05 (0.391)
Impact Subscale: Change at Month 12	-0.13 (0.400)
Impact Subscale: Change at Month 18	-0.10 (0.363)
Impact Subscale: Change at Month 24	-0.01 (0.335)
Impact Subscale: Change at Month 30	-0.10 (0.413)
Impact Subscale: Change at Month 36	0.00 (NA)
Impact Subscale: Change at EOT (up to Month 36)	-0.07 (0.377)

14. Secondary Outcome

Title	Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	FACT-Cog assessment was a 37-item tool with each item rated on a 5-point scale ranging from 0 to 4. It included 4 subscales: perceived cognitive impairments (CogPCI) (20 items, Item 1 - 20, score range 0-80), impact of perceived cognitive impairments on quality of life (CogQOL ) (4 items, Item 34 - 37, score range 0-16), comments from others (CogOth) (4 items, Item 21 - 24, score range 0-16) and perceived cognitive ability (CogPCA) (9 items, Item 25 - 33 score range 0-36). CogPCI subscale and comments from others subscale and two others subscale ranged as following: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit) and 4 (very much). For all four subscales of the FACT-cog: higher scores reflect worse cognitive function. Baseline (402): the last available pre-dose value in SHP634-402. EOT: the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description
Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	36
CogPCI: Change at Month 6	0.0 (6.88)
CogPCI: Change at Month 12	1.0 (9.28)
CogPCI: Change at Month 18	-1.4 (9.44)
CogPCI: Change at Month 24	-0.5 (9.35)
CogPCI: Change at Month 30	-0.3 (10.87)
CogPCI: Change at Month 36	-1.0 (NA)
CogPCI: Change at EOT (up to Month 36)	-0.4 (11.14)
CogQOL: Change at Month 6	-0.1 (2.27)
CogQOL: Change at Month 12	1.5 (2.92)
CogQOL: Change at Month 18	0.2 (3.16)
CogQOL: Change at Month 24	1.5 (3.63)
CogQOL: Change at Month 30	0.6 (3.20)
CogQOL: Change at Month 36	0.0 (NA)
CogQOL: Change at EOT (up to Month 36)	0.7 (3.20)
CogOth: Change at Month 6	0.0 (2.10)
CogOth: Change at Month 12	0.4 (1.85)
CogOth: Change at Month 18	0.7 (2.46)
CogOth: Change at Month 24	-0.2 (1.89)
CogOth: Change at Month 30	-0.2 (2.79)
CogOth: Change at Month 36	0.0 (NA)
CogOth: Change at EOT (up to Month 36)	0.2 (2.79)
CogPCA: Change at Month 6	-0.2 (2.60)
CogPCA: Change at Month 12	-1.1 (5.59)
CogPCA: Change at Month 18	-0.1 (5.12)
CogPCA: Change at Month 24	0.0 (4.41)
CogPCA: Change at Month 30	0.2 (6.62)
CogPCA: Change at Month 36	-2.0 (NA)
CogPCA: Change at EOT (up to Month 36)	0.3 (4.68)

15. Secondary Outcome

Title	Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	FACIT fatigue questionnaire contains 13 fatigue-related questions. The responses to the 13 items on the FACIT fatigue questionnaire was measured on a 4-point Likert scale (0-4). Thus, the total score ranges from 0 to 52. High scores represent less fatigue and better quality of life. For 2 questions, item 7 'I have energy' and item 8 'I am able to do my usual activities', the item response from questionnaire will be used as item score and no conversion is needed. For the rest of 11 questions, item score was calculated as 4- item response. Fatigue total score was calculated as: Fatigue Total Score = [sum of (item scores)]*13/ (number of items answered). Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description
Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	36
Change at Month 6	-1.41 (4.932)
Change at Month 12	0.10 (7.357)
Change at Month 18	-0.02 (7.467)
Change at Month 24	-0.13 (8.618)
Change at Month 30	-1.92 (10.777)
Change at Month 36	-1.00 (NA)
Change at EOT (up to Month 36)	-1.01 (8.171)

16. Secondary Outcome

Title	Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	The HADS was a 14-item scale that generates ordinal data. Seven of the items related to anxiety (Item 1, 3, 5, 7, 9, 11 and 13) and seven related to depression (Item 2, 4, 6, 8, 10, 12 and 14). The scale was designed to avoid reliance on aspects of conditions that are also common somatic symptoms of illness. Each item on the questionnaire was scored from 0-3, therefore, a person can score between 0 and 21 for either anxiety or depression. For each of the two sub-scores, if a participant obtain a score ranged from: 0 to 7, he is considered as "normal"; 8-10 = Borderline abnormal (borderline case) and 11-21 = Abnormal (case). Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	36
Anxiety Subscale: Change at Month 6	0.6 (2.39)
Anxiety Subscale: Change at Month 12	-0.5 (2.96)
Anxiety Subscale: Change at Month 18	-0.2 (3.74)
Anxiety Subscale: Change at Month 24	-1.5 (3.26)
Anxiety Subscale: Change at Month 30	-0.4 (3.21)
Anxiety Subscale: Change at Month 36	2.0 (NA)
Anxiety Subscale: Change at EOT (up to Month 36)	-0.4 (3.18)
Depression Subscale: Change at Month 6	0.4 (2.67)
Depression Subscale: Change at Month 12	-0.6 (2.61)
Depression Subscale: Change at Month 18	-0.8 (2.86)
Depression Subscale: Change at Month 24	-0.4 (3.84)
Depression Subscale: Change at Month 30	-1.0 (3.58)
Depression Subscale: Change at Month 36	1.0 (NA)
Depression Subscale: Change at EOT (up to Month 36)	-0.8 (3.35)

17. Secondary Outcome

Title	Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Description	SF-36 was a validated questionnaire that questions participants about perceived physical and mental health and function. SF-36 consisted of 8 scaled scores, which were weighted sums of the questions in their section. Each scale was directly transformed into 0-100 scale on the assumption that each question carries equal weight; A score of zero was equivalent to maximum disability and a score of 100 was equivalent to no disability. Eight sections included in SF-36 assessment: vitality (1=none of the time to 5=all of the time), physical functioning (1=yes, limited a lot to 3=no, not limited at all), bodily pain (1=very severe to 6=none), general health (1=poor to 5=excellent), physical role (1=all of the time to 5=none of the time), emotional role (1=all of the time to 5=none of the time), social role (1=all of the time: to 5=none of the time) and mental health (1=all of the time to 5=none of the time). Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Time Frame	Baseline (402), At Month 12, 24, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	33
Vitality: Change at Month 12	-0.11 (13.485)
Vitality: Change at Month 24	-3.27 (17.641)
Vitality: Change at Month 36	-5.00 (NA)
Vitality: Change at EOT (up to Month 36)	0.26 (18.006)
Physical functioning: Change at Month 12	1.61 (14.340)
Physical functioning: Change at Month 24	0.00 (13.676)
Physical functioning: Change at Month 36	0.00 (NA)
Physical functioning: Change at EOT (up to Month 36)	2.66 (20.398)
Bodily pain: Change at Month 12	6.55 (16.287)
Bodily pain: Change at Month 24	3.54 (13.948)
Bodily pain: Change at Month 36	0.00 (NA)
Bodily pain: Change at EOT (up to Month 36)	2.44 (15.546)
General health: Change at Month 12	3.28 (12.718)
General health: Change at Month 24	0.31 (13.033)
General health: Change at Month 36	0.00 (NA)
General health: Change at EOT (up to Month 36)	0.24 (11.755)
Physical role: Change at Month 12	-1.61 (29.535)
Physical role: Change at Month 24	-6.25 (31.641)
Physical role: Change at Month 36	0.00 (NA)
Physical role: Change at EOT (up to Month 36)	-5.47 (32.213)
Emotional role: Change at Month 12	-3.23 (31.453)
Emotional role: Change at Month 24	-2.38 (40.500)
Emotional role: Change at Month 36	0.00 (NA)
Emotional role: Change at EOT (up to Month 36)	-4.17 (45.398)
Social role: Change at Month 12	-3.23 (12.487)
Social role: Change at Month 24	-1.79 (19.159)
Social role: Change at Month 36	0.00 (NA)
Social role: Change at EOT (up to Month 36)	-1.17 (19.145)
Mental health: Change at Month 12	-0.26 (7.585)
Mental health: Change at Month 24	1.43 (12.845)
Mental health: Change at Month 36	4.00 (NA)
Mental health: Change at EOT (up to Month 36)	0.50 (12.801)

18. Secondary Outcome

Title	Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	Change from baseline in concentration of bone turnover markers included; Serum carboxy-terminal 4 telopeptide of type I collagen [s-CTX], procollagen type I amino-terminal propeptide [P1NP], osteocalcin, and sclerostin. Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	15
s-CTX: Change at Month 6	-0.082 (0.1053)
s-CTX: Change at Month 12	-0.190 (0.9847)
s-CTX: Change at Month 18	0.036 (0.3030)
s-CTX: Change at Month 24	0.201 (0.3985)
s-CTX: Change at Month 30	-0.204 (0.2896)
s-CTX: Change at EOT (up to Month 36)	-0.136 (0.5429)
P1NP: Change at Month 6	-3.12 (30.262)
P1NP: Change at Month 12	33.94 (55.080)
P1NP: Change at Month 18	31.06 (137.665)
P1NP: Change at Month 24	37.09 (152.162)
P1NP: Change at Month 30	30.95 (85.345)
P1NP: Change at EOT (up to Month 36)	80.90 (175.466)
Osteocalcin: Change at Month 6	-4.020 (11.6418)
Osteocalcin: Change at Month 12	-1.199 (44.2510)
Osteocalcin: Change at Month 18	-0.310 (43.7374)
Osteocalcin: Change at Month 24	23.483 (31.7005)
Osteocalcin: Change at Month 30	3.674 (36.8616)
Osteocalcin: Change at EOT (up to Month 36)	29.232 (65.9276)
Sclerostin: Change at Month 6	0.013 (0.1678)
Sclerostin: Change at Month 12	0.071 (0.1657)
Sclerostin: Change at Month 18	0.097 (0.2512)
Sclerostin: Change at Month 24	0.092 (0.1978)
Sclerostin: Change at Month 30	0.029 (0.1302)
Sclerostin: Change at EOT (up to Month 36)	0.075 (0.1651)

19. Secondary Outcome

Title	Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	Change from baseline in concentration of bone turnover markers included, bone specific alkaline phosphatase [BSAP] and tartrate-resistant acid phosphatase-5b (TRAP-5b). Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	15
BSAP: Change at Month 6	-1.194 (4.8791)
BSAP: Change at Month 12	4.310 (11.8965)
BSAP: Change at Month 18	4.824 (13.0980)
BSAP: Change at Month 24	11.546 (14.1455)
BSAP: Change at Month 30	2.124 (9.6951)
BSAP: Change at EOT (up to Month 36)	7.167 (12.4372)
TRAP-5b: Change at Month 6	-0.236 (0.7336)
TRAP-5b: Change at Month 12	0.946 (1.8702)
TRAP-5b: Change at Month 18	1.798 (4.3422)
TRAP-5b: Change at Month 24	2.347 (2.3850)
TRAP-5b: Change at Month 30	1.254 (4.2890)
TRAP-5b: Change at EOT (up to Month 36)	1.336 (3.2241)

20. Secondary Outcome

Title	Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	Change from baseline in bone architecture was assessed by using DXA. The DXA scans was evaluated for BMD of the lumbar spine (vertebra L1, L2, L3, L4), total hip and femoral neck, and distal radius. Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Time Frame	Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	24
Lumbar Spine Total: Change at Month 6	-0.027 (0.0386)
Lumbar Spine Total: Change at Month 12	-0.020 (0.0398)
Lumbar Spine Total: Change at Month 18	-0.012 (0.0385)
Lumbar Spine Total: Change at Month 24	-0.008 (0.0545)
Lumbar Spine Total: Change at Month 30	-0.021 (0.0549)
Lumbar Spine Total: Change at EOT (up to Month 36)	-0.024 (0.0524)
Lumbar L1: Change at Month 6	0.000 (0.0334)
Lumbar L1: Change at Month 12	0.001 (0.0374)
Lumbar L1: Change at Month 18	0.003 (0.0426)
Lumbar L1: Change at Month 24	0.018 (0.0552)
Lumbar L1: Change at Month 30	-0.006 (0.0656)
Lumbar L1: Change at EOT (up to Month 36)	0.005 (0.0641)
Lumbar L2: Change at Month 6	-0.020 (0.0276)
Lumbar L2: Change at Month 12	-0.017 (0.0399)
Lumbar L2: Change at Month 18	-0.006 (0.0428)
Lumbar L2: Change at Month 24	-0.001 (0.0518)
Lumbar L2: Change at Month 30	-0.012 (0.0560)
Lumbar L2: Change at EOT (up to Month 36)	-0.018 (0.0487)
Lumbar L3: Change at Month 6	-0.018 (0.0325)
Lumbar L3: Change at Month 12	-0.015 (0.0466)
Lumbar L3: Change at Month 18	-0.012 (0.0538)
Lumbar L3: Change at Month 24	-0.001 (0.0495)
Lumbar L3: Change at Month 30	-0.013 (0.0478)
Lumbar L3: Change at EOT (up to Month 36)	-0.016 (0.0541)
Lumbar L4: Change at Month 6	-0.015 (0.0328)
Lumbar L4: Change at Month 12	-0.010 (0.0362)
Lumbar L4: Change at Month 18	-0.013 (0.0319)
Lumbar L4: Change at Month 24	-0.004 (0.0546)
Lumbar L4: Change at Month 30	-0.014 (0.0513)
Lumbar L4: Change at EOT (up to Month 36)	-0.023 (0.0497)
Femoral Neck: Change at Month 6	-0.010 (0.0468)
Femoral Neck: Change at Month 12	-0.027 (0.0470)
Femoral Neck: Change at Month 18	-0.025 (0.0543)
Femoral Neck: Change at Month 24	-0.032 (0.0574)
Femoral Neck: Change at Month 30	-0.020 (0.0483)
Femoral Neck: Change at EOT (up to Month 36)	-0.018 (0.0467)
Total Hip: Change at Month 6	-0.005 (0.0213)
Total Hip: Change at Month 12	-0.004 (0.0224)
Total Hip: Change at Month 18	-0.001 (0.0293)
Total Hip: Change at Month 24	-0.008 (0.0299)
Total Hip: Change at Month 30	-0.003 (0.0359)
Total Hip: Change at EOT (up to Month 36)	-0.013 (0.0358)
Distal Radius: Change at Month 6	0.032 (0.1204)
Distal Radius: Change at Month 12	0.018 (0.1104)
Distal Radius: Change at Month 18	0.020 (0.1193)
Distal Radius: Change at Month 24	0.024 (0.1278)
Distal Radius: Change at Month 30	0.024 (0.1276)
Distal Radius: Change at EOT (up to Month 36)	0.011 (0.1049)

21. Secondary Outcome

Title	Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	Change from baseline in bone architecture was assessed by using DXA. The DXA scans was evaluated for Total T-score of the lumbar spine (vertebra L1-L4), hip (total and femoral neck), and ⅓ distal radius. Baseline (402) was defined as the last available pre-dose value in SHP634-402. The T-score was a comparison of a person's bone density with that of a healthy 30-year-old adult of the same sex and ethnicity. T-score included: Normal: >= -1; Osteopenia: < -1 and > -2.5; Osteoporosis: <= -2.5. A lower T-score implies a lower bone mineral density. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Time Frame	Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	24
Lumbar Spine Total: Change at Month 6	-0.16 (0.343)
Lumbar Spine Total: Change at Month 12	-0.12 (0.331)
Lumbar Spine Total: Change at Month 18	-0.09 (0.338)
Lumbar Spine Total: Change at Month 24	-0.04 (0.477)
Lumbar Spine Total: Change at Month 30	-0.16 (0.506)
Lumbar Spine Total: Change at EOT (up to Month 36)	-0.18 (0.476)
Lumbar Spine L1: Change at Month 6	-0.01 (0.293)
Lumbar Spine L1: Change at Month 12	0.01 (0.346)
Lumbar Spine L1: Change at Month 18	0.01 (0.394)
Lumbar Spine L1: Change at Month 24	0.16 (0.508)
Lumbar Spine L1: Change at Month 30	-0.05 (0.598)
Lumbar Spine L1: Change at Month EOT (up to Month 36)	0.04 (0.588)
Lumbar Spine L2: Change at Month 6	-0.17 (0.243)
Lumbar Spine L2: Change at Month 12	-0.15 (0.361)
Lumbar Spine L2: Change at Month 18	-0.05 (0.394)
Lumbar Spine L2: Change at Month 24	0.01 (0.477)
Lumbar Spine L2: Change at Month 30	-0.10 (0.512)
Lumbar Spine L2: Change at EOT (up to Month 36)	-0.15 (0.440)
Lumbar Spine L3: Change at Month 6	-0.16 (0.304)
Lumbar Spine L3: Change at Month 12	-0.12 (0.424)
Lumbar Spine L3: Change at Month 18	-0.10 (0.518)
Lumbar Spine L3: Change at Month 24	0.03 (0.468)
Lumbar Spine L3: Change at Month 30	-0.11 (0.461)
Lumbar Spine L3: Change at EOT (up to Month 36)	-0.14 (0.509)
Lumbar Spine L4: Change at Month 6	-0.13 (0.287)
Lumbar Spine L4: Change at Month 12	-0.09 (0.336)
Lumbar Spine L4: Change at Month 18	-0.12 (0.306)
Lumbar Spine L4: Change at Month 24	-0.04 (0.484)
Lumbar Spine L4: Change at Month 30	-0.14 (0.479)
Lumbar Spine L4: Change at EOT (up to Month 36)	-0.21 (0.456)
Femoral Neck: Change at Month 6	-0.06 (0.386)
Femoral Neck: Change at Month 12	-0.21 (0.390)
Femoral Neck: Change at Month 18	-0.21 (0.448)
Femoral Neck: Change at Month 24	-0.26 (0.462)
Femoral Neck: Change at Month 30	-0.17 (0.451)
Femoral Neck: Change at EOT (up to Month 36)	-0.16 (0.427)
Total Hip: Change at Month 6	-0.02 (0.194)
Total Hip: Change at Month 12	-0.03 (0.200)
Total Hip: Change at Month 18	0.00 (0.240)
Total Hip: Change at Month 24	-0.07 (0.274)
Total Hip: Change at Month 30	-0.02 (0.306)
Total Hip: Change at EOT (up to Month 36)	-0.10 (0.304)
Distal 1/3 Radius: Change at Month 6	0.00 (0.408)
Distal 1/3 Radius: Change at Month 12	-0.09 (0.332)
Distal 1/3 Radius: Change at Month 18	-0.07 (0.385)
Distal 1/3 Radius: Change at Month 24	-0.11 (0.342)
Distal 1/3 Radius: Change at Month 30	-0.16 (0.462)
Distal 1/3 Radius: Change at EOT (up to Month 36)	-0.22 (0.359)

22. Secondary Outcome

Title	Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Description	Change from baseline in bone architecture was assessed by using HRpQCT. The HRpQCT analyses included both radius and tibia of total area position. Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Time Frame	Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	28
Total Area Position: Radius, Change at Month 6	-2.99 (12.143)
Total Area Position: Radius, Change at Month 12	-1.36 (9.358)
Total Area Position: Radius, Change at Month 18	-3.59 (12.111)
Total Area Position: Radius, Change at Month 24	-5.31 (13.761)
Total Area Position: Radius, Change at Month 30	-6.64 (15.009)
Total Area Position: Radius, Change at EOT (up to Month 36)	-2.21 (13.908)
Total Area Position: Tibia, Change at Month 6	-5.34 (20.594)
Total Area Position: Tibia, Change at Month 12	-2.10 (2.941)
Total Area Position: Tibia, Change at Month 18	-6.02 (16.858)
Total Area Position: Tibia, Change at Month 24	-6.71 (17.861)
Total Area Position: Tibia, Change at Month 30	-0.93 (6.703)
Total Area Position: Tibia, Change at EOT (up to Month 36)	-1.21 (6.391)

23. Secondary Outcome

Title	Mean Bone Histology (Biopsy) of Adjusted Apposition Rate and Cancellous Minimum Apposition Rate at Month 12, and EOT (up to Month 36)
Description	Bone histology parameters consisted of adjusted apposition rate and cancellous minimum apposition rate. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	At Month 12, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Safety population consisted of all enrolled participants who received at least dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 [NCT01199614] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	4
Adjusted Apposition rate: At Month 12	0.207 (0.2043)
Adjusted Apposition rate: At EOT (up to Month 36)	0.273 (0.2125)
Cancellous Min Apposition Rate: At Month 12	0.453 (0.1604)
Cancellous Min Apposition Rate: At EOT (up to Month 36)	0.485 (0.1455)

24. Secondary Outcome

Title	Mean Bone Histology (Biopsy) of Bone Formation Rate at Month 12, and EOT (up to Month 36)
Description	Bone histology parameters consisted of bone formation rate. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, "mcm^3/mcm^2/d" is abbreviated as micro cubic meter per micro square meter per day.
Time Frame	At Month 12, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	4
Bone Formation Rate: At Month 12	0.0360 (0.04233)
Bone Formation Rate: At EOT (up to Month 36)	0.0665 (0.07011)

25. Secondary Outcome

Title	Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
Description	Bone histology parameters consisted of cancellous bone volume, cancellous eroded surface, cancellous mineral surface, and cancellous osteoid surface. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	At Month 12, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	4
Cancellous Bone Volume: At Month 12	32.863 (9.3280)
Cancellous Bone Volume: At EOT (up to Month 36)	34.988 (8.7210)
Cancellous Eroded Surface: At Month 12	10.373 (5.1763)
Cancellous Eroded Surface: At EOT (up to Month 36)	12.575 (6.1034)
Cancellous Mineral Surface: At Month 12	6.973 (6.3212)
Cancellous Mineral Surface: At EOT (up to Month 36)	12.028 (11.3497)
Cancellous Osteoid Surface: At Month 12	17.863 (14.2300)
Cancellous Osteoid Surface: At EOT (up to Month 36)	21.803 (14.0379)

26. Secondary Outcome

Title	Mean Bone Histology (Biopsy) of Cancellous Osteoid Thickness and Cortical Width at Month 12, and EOT (up to Month 36)
Description	Bone histology parameters consisted of cancellous osteoid thickness and cortical width. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Time Frame	At Month 12, and EOT (up to Month 36)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
Measure Participants	4
Cancellous Osteoid Thickness: At Month 12	6.667 (2.9913)
Cancellous Osteoid Thickness: At EOT (up to Month 36)	6.667 (2.9913)
Cortical Width: At Month 12	668.677 (277.1239)
Cortical Width: At EOT (up to Month 36)	698.913 (234.2120)

Adverse Events

	rhPTH(1-84)
Time Frame	From start of study drug administration up to end of study (up to 38 months)
Adverse Event Reporting Description

Arm/Group Title	rhPTH(1-84)
Arm/Group Description	Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter [mg/dL]).
All Cause Mortality
	Affected / at Risk (%)	# Events
Total	0/39 (0%)
Serious Adverse Events
	rhPTH(1-84)
	Affected / at Risk (%)	# Events
Total	6/39 (15.4%)
Cardiac disorders
Angina pectoris	1/39 (2.6%)	1
Gastrointestinal disorders
Hiatus hernia	1/39 (2.6%)	1
Hepatobiliary disorders
Cholecystitis	1/39 (2.6%)	1
Infections and infestations
Clostridium difficile colitis	1/39 (2.6%)	2
Gastroenteritis	1/39 (2.6%)	1
Post procedural infection	1/39 (2.6%)	1
Pyelonephritis	1/39 (2.6%)	1
Upper respiratory tract infection	1/39 (2.6%)	1
Urinary tract infection	1/39 (2.6%)	1
Injury, poisoning and procedural complications
Hypobarism	1/39 (2.6%)	1
Joint dislocation	1/39 (2.6%)	1
Metabolism and nutrition disorders
Hyperkalaemia	1/39 (2.6%)	1
Hypocalcaemia	3/39 (7.7%)	8
Hypomagnesaemia	1/39 (2.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/39 (2.6%)	1
Other (Not Including Serious) Adverse Events
	rhPTH(1-84)
	Affected / at Risk (%)	# Events
Total	34/39 (87.2%)
Endocrine disorders
Hypothyroidism	2/39 (5.1%)	2
Gastrointestinal disorders
Constipation	3/39 (7.7%)	4
Diarrhoea	2/39 (5.1%)	2
Gastrooesophageal reflux disease	2/39 (5.1%)	2
Nausea	4/39 (10.3%)	5
Immune system disorders
Drug hypersensitivity	2/39 (5.1%)	2
Seasonal allergy	2/39 (5.1%)	2
Infections and infestations
Bronchitis	3/39 (7.7%)	4
Influenza	5/39 (12.8%)	5
Nasopharyngitis	2/39 (5.1%)	2
Pharyngitis streptococcal	5/39 (12.8%)	6
Pneumonia	2/39 (5.1%)	2
Sinusitis	2/39 (5.1%)	2
Tooth infection	2/39 (5.1%)	2
Urinary tract infection	5/39 (12.8%)	5
Injury, poisoning and procedural complications
Foot fracture	2/39 (5.1%)	2
Hand fracture	2/39 (5.1%)	2
Ligament rupture	2/39 (5.1%)	2
Meniscus injury	2/39 (5.1%)	2
Investigations
Alanine aminotransferase increased	2/39 (5.1%)	2
Aspartate aminotransferase increased	2/39 (5.1%)	2
Metabolism and nutrition disorders
Hyperlipidaemia	2/39 (5.1%)	2
Hypocalcaemia	10/39 (25.6%)	17
Hypokalaemia	3/39 (7.7%)	5
Hypomagnesaemia	2/39 (5.1%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	3/39 (7.7%)	4
Muscle spasms	2/39 (5.1%)	2
Myalgia	2/39 (5.1%)	2
Pain in extremity	3/39 (7.7%)	3
Nervous system disorders
Headache	2/39 (5.1%)	2
Hypoaesthesia	2/39 (5.1%)	2
Psychiatric disorders
Anxiety	16/39 (41%)	17
Depression	8/39 (20.5%)	8
Insomnia	2/39 (5.1%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/39 (5.1%)	2
Dyspnoea	2/39 (5.1%)	2
Sleep apnoea syndrome	2/39 (5.1%)	2
Skin and subcutaneous tissue disorders
Dermatitis allergic	2/39 (5.1%)	2
Vascular disorders
Hypertension	6/39 (15.4%)	7
Varicose vein	2/39 (5.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Responsible Party:

Shire

ClinicalTrials.gov Identifier:

NCT02910466

Other Study ID Numbers:

SHP634-402

First Posted:

Sep 22, 2016

Last Update Posted:

Jul 28, 2021

Last Verified:

Jul 1, 2021

A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism

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