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

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)

Population: 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.

Baseline (402) was defined as the last available pre-dose value in SHP634-402.

Time frame: Baseline (402), Month 12

Population: 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.

Baseline (402) was defined as the last available pre-dose value in SHP634-402.

Time frame: Baseline (402), Month 18

Population: 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.

Baseline (402) was defined as the last available pre-dose value in SHP634-402.

Time frame: Baseline (402), Month 24

Population: 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.

Baseline (402) was defined as the last available pre-dose value in SHP634-402.

Time frame: Baseline (402), Month 30

Population: 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.

Baseline (402) was defined as the last available pre-dose value in SHP634-402.

Time frame: Baseline (402), Month 36

Population: 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.

Baseline (402) was defined as the last available pre-dose value in SHP634-402.

Time frame: Baseline (402), Month 6

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.