Trial Outcomes & Findings for A Study to Learn if Recombinant Human Parathyroid Hormone [rhPTH(1-84)] Can Improve Symptoms and Metabolic Control in Adults With Hypoparathyroidism (BALANCE) (NCT NCT03324880)

Results Overview

The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The symptom subscale score was computed as the average of symptom items 1-7 scores with more than 3 of the 7 symptom item scores were non-missing. Negative change in scores indicates improvement. A mixed model for repeated measures (MMRM) was used for analysis.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

93 participants

Primary outcome timeframe

Baseline, Week 26

Results posted on

2023-06-09

Participant Flow

Participants took part in the study at 35 investigative sites in Belgium, Canada, Denmark, Spain, France, United Kingdom, Italy, Netherlands, Norway, Portugal, Sweden and the United States (US) from 24 January 2018 to 19 May 2022.

Participants with a diagnosis of symptomatic hypoparathyroidism were enrolled in 1:1 ratio to receive placebo matching rhPTH (1-84) with active vitamin D and/or calcium supplements or rhPTH (1-84) with active vitamin D and/or calcium supplements.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to rhPTH (1-84) as subcutaneous (SC) injection once daily (QD) with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) Participants received rhPTH (1-84) 50 microgram (mcg) SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Overall Study STARTED	48	45
Overall Study COMPLETED	46	39
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to rhPTH (1-84) as subcutaneous (SC) injection once daily (QD) with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) Participants received rhPTH (1-84) 50 microgram (mcg) SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Overall Study Adverse Event	0	2
Overall Study Withdrawal by Subject	2	2
Overall Study Lost to Follow-up	0	1
Overall Study Product Recall	0	1

Baseline Characteristics

Number analyzed is the number of participants with data available for analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=48 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=45 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.	Total n=93 Participants Total of all reporting groups
Age, Continuous	49.2 years STANDARD_DEVIATION 12.16 • n=48 Participants	47.8 years STANDARD_DEVIATION 10.41 • n=45 Participants	48.5 years STANDARD_DEVIATION 11.31 • n=93 Participants
Sex: Female, Male Female	40 Participants n=48 Participants	42 Participants n=45 Participants	82 Participants n=93 Participants
Sex: Female, Male Male	8 Participants n=48 Participants	3 Participants n=45 Participants	11 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=48 Participants	3 Participants n=45 Participants	7 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=48 Participants	31 Participants n=45 Participants	70 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=48 Participants	11 Participants n=45 Participants	16 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=48 Participants	0 Participants n=45 Participants	0 Participants n=93 Participants
Race (NIH/OMB) Asian	1 Participants n=48 Participants	2 Participants n=45 Participants	3 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=48 Participants	0 Participants n=45 Participants	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=48 Participants	0 Participants n=45 Participants	0 Participants n=93 Participants
Race (NIH/OMB) White	47 Participants n=48 Participants	43 Participants n=45 Participants	90 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=48 Participants	0 Participants n=45 Participants	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=48 Participants	0 Participants n=45 Participants	0 Participants n=93 Participants
Hypoparathyroidism Symptom Diary (HPT-SD/HypoPT-SD) Symptom Subscale Score at Baseline	2.23 score on a scale STANDARD_DEVIATION 0.541 • n=47 Participants • Number analyzed is the number of participants with data available for analysis.	2.56 score on a scale STANDARD_DEVIATION 0.728 • n=45 Participants • Number analyzed is the number of participants with data available for analysis.	2.39 score on a scale STANDARD_DEVIATION 0.657 • n=92 Participants • Number analyzed is the number of participants with data available for analysis.

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The symptom subscale score was computed as the average of symptom items 1-7 scores with more than 3 of the 7 symptom item scores were non-missing. Negative change in scores indicates improvement. A mixed model for repeated measures (MMRM) was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=30 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Subscale Score at Week 26	-0.93 score on a scale Standard Error 0.130	-1.46 score on a scale Standard Error 0.137

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire contains 13 fatigue-related questions. The responses to the 13 items on the FACIT-Fatigue questionnaire are each measured on a 5-point Likert scale, where 0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit and 4=Very much. Thus, the total score ranges from 0 to 52. High scores represent less fatigue. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=28 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 26	4.4 score on a scale Standard Error 1.87	15.0 score on a scale Standard Error 1.93

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The SF-36 is a validated instrument that questions participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. Change in PCS derived from SF-36v2 at Week 26 was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=29 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Physical Component Summary (PCS) Derived From 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores at Week 26	4.404 score on a scale Standard Error 1.3514	8.646 score on a scale Standard Error 1.3406

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The impact subscale score was computed as the average of impact items 10-13 scores with no impact item score was non-missing. Negative change in scores indicates improvement. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=30 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Subscale Score at Week 26	-0.36 score on a scale Standard Error 0.076	-0.69 score on a scale Standard Error 0.081

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The change in individual symptom item scores was reported. Negative change in scores indicates improvement. MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=30 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Items Score at Week 26 Impact on Sleep	-0.39 score on a scale Standard Error 0.086	-0.68 score on a scale Standard Error 0.090
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Items Score at Week 26 Ability to Exercise	-0.35 score on a scale Standard Error 0.088	-0.71 score on a scale Standard Error 0.093
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Items Score at Week 26 Ability to Complete Work	-0.39 score on a scale Standard Error 0.084	-0.76 score on a scale Standard Error 0.089
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Items Score at Week 26 Impact Family Relationships	-0.29 score on a scale Standard Error 0.083	-0.66 score on a scale Standard Error 0.088

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. The anxiety item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the anxiety item score was set to missing. Negative change in scores indicates improvement. MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=30 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Anxiety (Item 8) Score at Week 26	-0.79 score on a scale Standard Error 0.139	-1.35 score on a scale Standard Error 0.147

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. The sadness or depression item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the item score was set to missing. Negative change in scores indicates improvement. MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=30 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Sadness or Depression (Item 9) Score at Week 26	-0.76 score on a scale Standard Error 0.137	-1.30 score on a scale Standard Error 0.145

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. Negative change in scores indicates improvement. MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=30 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Scores at Week 26 Muscle Cramps	-0.91 score on a scale Standard Error 0.150	-1.47 score on a scale Standard Error 0.158
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Scores at Week 26 Tingling	-1.04 score on a scale Standard Error 0.146	-1.58 score on a scale Standard Error 0.154
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Scores at Week 26 Numbness	-0.89 score on a scale Standard Error 0.158	-1.37 score on a scale Standard Error 0.167
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Scores at Week 26 Muscle Spasms	-0.87 score on a scale Standard Error 0.149	-1.49 score on a scale Standard Error 0.159
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Scores at Week 26 Feelings of Heaviness	-0.96 score on a scale Standard Error 0.157	-1.34 score on a scale Standard Error 0.166
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Scores at Week 26 Physical Fatigue	-0.89 score on a scale Standard Error 0.155	-1.45 score on a scale Standard Error 0.165
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Scores at Week 26 Brain Fog	-0.90 score on a scale Standard Error 0.127	-1.40 score on a scale Standard Error 0.134

SECONDARY outcome

Timeframe: Baseline up to Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

Response was defined as a 30% reduction in HypoPT-SD symptom subscale score from baseline. The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; and for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The symptom subscale score was computed as the average of symptom items 1-7 scores with more than 3 of the 7 symptom item scores were non-missing. Data reported also includes results for early terminated participants.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=32 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Number of Participants With Response at Week 26 [Early Termination (ET)]	24 Participants	25 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The Most Bothersome Symptom Score was analyzed. Negative change in scores indicates improvement. MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=26 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in the Most Bothersome Symptom Score at Week 26	-0.87 score on a scale Standard Error 0.156	-1.77 score on a scale Standard Error 0.174

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) assessment is a 37-item instrument. The perceived cognitive impairment and the impact on quality of life domains were assessed in this study. These 2 domains include 22 items rated on a 5-point scale. The perceived cognitive impairments subscale contains 18 items and each item has a 5-point ordinal response scale (0=Never, 1= About once a week, 2 = Two to three times a week, 3= Nearly every day, 4 = Several times a day). Each item score is calculated as (4 minus item response), and the subscale score is \[sum of (4 minus item response)\]\*18/(number of items answered)\]. The perceived cognitive impairment subscale score ranges from 0 to 72, with higher scores indicate better cognitive function. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=28 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Perceived Cognitive Impairments (PCI) Score at Week 26	2.7 score on a scale Standard Error 0.74	4.8 score on a scale Standard Error 0.76

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) assessment is a 37-item instrument. The perceived cognitive impairment and the impact on quality of life domains were assessed in this study. These 2 domains include 22 items rated on a 5-point scale. The impact on quality of life domain contains 4 items and each item has a 5-point ordinal response scale (0=Never, 1= About once a week, 2 = Two to three times a week, 3= Nearly every day, 4 = Several times a day). Each item score is calculated as (4 minus item response), and the subscale score is \[sum of (4 minus item response)\]\*4/(number of items answered)\]. The impact on quality of life subscale score ranges from 0 to 16 with higher score indicates better cognitive function. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=28 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Impact on Quality of Life (QoL) Score at Week 26	2.7 score on a scale Standard Error 0.74	4.8 score on a scale Standard Error 0.76

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available analysis for specified categories.

The SF-36 is a validated instruments that question participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. Change in the score of individual domains of SF-36v2 at Week 26 was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=29 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 Standard-Social Functioning	6.005 score on a scale Standard Error 1.8636	9.814 score on a scale Standard Error 1.8661
Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 Standard-Bodily Pain	4.194 score on a scale Standard Error 1.4987	11.404 score on a scale Standard Error 1.4919
Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 Standard-General Health	3.515 score on a scale Standard Error 1.4509	9.061 score on a scale Standard Error 1.4463
Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 Standard-Mental Health	3.719 score on a scale Standard Error 1.6098	11.576 score on a scale Standard Error 1.6043
Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 Standard-Physical Functioning	4.833 score on a scale Standard Error 1.4850	9.387 score on a scale Standard Error 1.4669
Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 Standard-Role-Emotional	5.228 score on a scale Standard Error 1.6322	13.648 score on a scale Standard Error 1.6254
Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 Standard-Role-Physical	5.964 score on a scale Standard Error 1.5799	10.194 score on a scale Standard Error 1.5670
Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 Standard-Vitality	4.205 score on a scale Standard Error 1.6539	12.147 score on a scale Standard Error 1.6547

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The SF-36 is a validated instruments that question participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. Change in the MCS of SF-36v2 at Week 26 was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=29 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Mental Component Summary (MCS) Score of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26	4.297 score on a scale Standard Error 1.5898	12.597 score on a scale Standard Error 1.5904

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses. Number analyzed is the number of participants with data available for analysis for specified categories.

WPAI assessed impact of HypoPT on work productivity and daily activities. Concepts that WPAI: Hypoparathyroidism measures include time missed from work and impairment of work and other regular activities due to specific health problem (HypoPT). WPI was calculated based on 4 items including Q2: hours of work missed due to HPT; Q4: actual hours worked; Q5: HPT effect on productivity at work; Q6: HPT effect on daily activities. Scores for 4 subscales were calculated as Percent work time missed due to problem: Q2/(Q2+Q4)\*100; Percent impairment while working due to problem: Q5/10\*100; Percent overall work impairment due to problem: Q2/(Q2+Q4)+\[(1(Q2/(Q2+Q4)))x(Q5/10)\]\*100; Percent activity impairment due to problem: Q6/10\*100. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. Change from baseline in questionnaire response was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=27 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Hypoparathyroidism (WPAI: Hypoparathyroidism) Score at Week 26 Percent Impairment While Working Due to Problem	-11.7 score on a scale Standard Error 4.79	-26.3 score on a scale Standard Error 5.76
Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Hypoparathyroidism (WPAI: Hypoparathyroidism) Score at Week 26 Percent Overall Work Impairment Due to Problem	-11.17 score on a scale Standard Error 3.854	-26.08 score on a scale Standard Error 4.774
Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Hypoparathyroidism (WPAI: Hypoparathyroidism) Score at Week 26 Percent Activity Impairment Due to Problem	-10.2 score on a scale Standard Error 3.97	-23.3 score on a scale Standard Error 4.17
Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Hypoparathyroidism (WPAI: Hypoparathyroidism) Score at Week 26 Percent Work Time Missed Due to Problem	2.30 score on a scale Standard Error 6.279	5.43 score on a scale Standard Error 7.155

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The PGI-S is a global index that can be used to rate the severity of a specific condition. The PGI-S is a rating scale that asks the respondent to best describe how their symptoms severity. Response options are assessed as per 5-point scale: no symptoms (0), mild (1), moderate (2), severe (3), and very severe (4). Mean change in scores of PGI-S at Week 26 was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=29 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Severity (PGI-S) at Week 26	-0.8 score on a scale Standard Error 0.15	-1.4 score on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

The PGI-C is verbal rating scale asks the respondent to best describe change in symptoms compared to the beginning of study. Response options are assessed using a 7-point scale: very much improved (0), much improved (1), minimally improved (2), no change (3), minimally worse (4), much worse (5), and very much worse (6). Negative change indicates improvement. Mean change in scores of PGI-C at Week 26 was be reported.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=28 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Change (PGI-C) at Week 26	-0.6 score on a scale Standard Deviation 1.04	-1.7 score on a scale Standard Deviation 1.63

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses. Number analyzed is the number of participants with data available for analysis for specified categories.

Neurocognitive test battery included tests evaluating frontal-executive domain, which encompasses functions attributable to prefrontal cortex and its connections to basal ganglia (mostly striatum). Tests included the CogState (CS) Brief Battery (including the Detection: speed \[range from 2.001 to 6; lower scores (LS) indicate improvement (IMP)\], Identification: speed \[range from 2.001 to 6; LS indicate IMP\], One Card Learning: accuracy \[range from 0 to 1.5708; higher scores (HS) indicate IMP\], One Back: speed \[range from 2.001 to 6; LS indicate IMP\]), CS Groton Maze Learning Test: total errors (range from 0 to infinity; LS indicate IMP), CS International Shopping List Task (ISLT): number of correct responses (range from 0 to infinity; HS indicate IMP), and CS ISLT -Delayed Recall: number of correct responses (range from 0 to infinity; HS indicate IMP). Change in in-clinic neurocognitive assessment scores at Week 24 was reported. Analysis of Covariance (ANCOVA) was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=30 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 Detection	0.03 score on a scale Interval 0.01 to 0.06	0.05 score on a scale Interval 0.02 to 0.08
Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 One Card Learning	0.12 score on a scale Interval 0.07 to 0.16	0.13 score on a scale Interval 0.08 to 0.17
Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 One Back (ONB)	0.09 score on a scale Interval 0.06 to 0.12	0.09 score on a scale Interval 0.06 to 0.13
Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 Groton Maze Learning (GML)	-2.43 score on a scale Interval -9.89 to 5.02	7.49 score on a scale Interval -0.46 to 15.45
Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 International Shopping List (ISL)	1.98 score on a scale Interval 0.73 to 3.24	1.42 score on a scale Interval 0.08 to 2.76
Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 International Shopping List Test Delayed Recall (ISRL)	1.31 score on a scale Interval 0.62 to 1.99	1.86 score on a scale Interval 1.13 to 2.59
Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 Identification	0.02 score on a scale Interval -0.01 to 0.05	0.04 score on a scale Interval 0.01 to 0.07

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses. Number analyzed is the number of participants with data available for analysis for specified categories.

Neurocognitive test battery included tests evaluating frontal-executive domain, which encompasses functions attributable to prefrontal cortex and its connections to basal ganglia (mostly striatum). Tests included the CogState (CS) Brief Battery (including the Detection: speed \[range from 2.001 to 6; lower scores (LS) indicate improvement (IMP)\], Identification: speed \[range from 2.001 to 6; LS indicate IMP\], One Card Learning: accuracy \[range from 0 to 1.5708; higher scores (HS) indicate IMP\], One Back: speed \[range from 2.001 to 6; LS indicate IMP\]). Changes in at-home neurocognitive assessment scores (CS Brief Battery) at Week 26 was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=38 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in At-Home Neurocognitive Assessment Scores at Week 26 Detection (DET)	-0.01 score on a scale Interval -0.03 to 0.0	-0.01 score on a scale Interval -0.03 to 0.01
Change From Baseline in At-Home Neurocognitive Assessment Scores at Week 26 Identification (IDN)	-0.01 score on a scale Interval -0.03 to 0.01	0.00 score on a scale Interval -0.02 to 0.02
Change From Baseline in At-Home Neurocognitive Assessment Scores at Week 26 One Card Learning (OCL)	0.08 score on a scale Interval 0.05 to 0.11	0.09 score on a scale Interval 0.06 to 0.12
Change From Baseline in At-Home Neurocognitive Assessment Scores at Week 26 One Back (ONB)	0.02 score on a scale Interval 0.0 to 0.04	0.03 score on a scale Interval 0.01 to 0.05

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

Change in 24-hour urine calcium excretion at Week 26 was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=33 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in 24-hour Urine Calcium Excretion at Week 26	-1.99 millimoles per day (mmol/day) Standard Error 0.574	0.11 millimoles per day (mmol/day) Standard Error 0.651

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

Change in serum phosphate level at Week 26 was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=40 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Serum Phosphate Level at Week 26	0.030 millimoles per liter (mmol/L) Standard Error 0.0270	-0.145 millimoles per liter (mmol/L) Standard Error 0.0289

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

Changes in doses of active vitamin D at Week 26 was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=38 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Doses of Active Vitamin D at Week 26	-5.65 micrograms per day (μg/day) Standard Error 3.155	-1.57 micrograms per day (μg/day) Standard Error 3.418

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

Changes in doses of calcium supplements at Week 26 was reported. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=40 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Doses of Calcium Supplements at Week 26	-44.3 milligrams per day (mg/day) Standard Error 91.13	-375.6 milligrams per day (mg/day) Standard Error 96.20

SECONDARY outcome

Timeframe: Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

Change From Baseline in albumin-corrected serum calcium between 1.875 millimoles per liter (mmol/L) (7.5 milligram per deciliter \[mg/dL\]) and upper limit of normal (ULN) for the central laboratory normal range at Week 26 was reported.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=40 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Albumin-corrected Serum Calcium Control at Week 26	-0.033 mmol/L Standard Deviation 0.2072	0.090 mmol/L Standard Deviation 0.2254

SECONDARY outcome

Timeframe: Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

Number of participants achieving composite criteria of the following: albumin-corrected serum calcium between 1.875 mmol/L (7.5 mg/dL) and the ULN for the central laboratory normal range, dose of active vitamin D decreased by 50% and at least a 50% reduction from the baseline oral elemental calcium supplement dose at Week 26 was reported.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=40 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Number of Participants Who Achieve Composite Criteria for Albumin-corrected Serum Calcium Concentration, Active Vitamin D Dose and Oral Elemental Calcium Supplement Dose at Week 26	6 Participants	21 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

Bone turnover markers included serum bone-specific alkaline phosphatase, procollagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=37 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Bone Turnover Marker Bone Specific Alkaline Phosphatase at Week 26	0.69 units per liter (U/L) Standard Error 2.256	23.03 units per liter (U/L) Standard Error 2.365

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available at the time of analyses.

Bone turnover markers included serum bone-specific alkaline phosphatase, procollagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=36 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Bone Turnover Marker Type I Collagen C-Telopeptides at Week 26	-5.0 nanograms per liter (ng/L) Standard Error 76.52	780.5 nanograms per liter (ng/L) Standard Error 84.00

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Set included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available analysis for specified categories.

Bone turnover markers included serum bone-specific alkaline phosphatase, procollagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin. A MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=36 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Change From Baseline in Bone Turnover Marker Osteocalcin and Procollagen 1 N-Terminal Propeptide at Week 26 Osteocalcin	-0.88 micrograms per liter (µg/L) Standard Error 4.109	55.55 micrograms per liter (µg/L) Standard Error 4.476
Change From Baseline in Bone Turnover Marker Osteocalcin and Procollagen 1 N-Terminal Propeptide at Week 26 Procollagen 1 N-Terminal Propeptide	1.95 micrograms per liter (µg/L) Standard Error 22.744	228.52 micrograms per liter (µg/L) Standard Error 24.475

SECONDARY outcome

Timeframe: From start of study drug administration to 4 weeks post follow-up (up to Week 36)

Population: Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as AEs that started or worsened on or after the date and time of the first dose of investigational product.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=45 Participants Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	46 Participants	41 Participants

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 41 other events

Deaths: 0 deaths

rhPTH (1-84)

Serious events: 6 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=48 participants at risk Participants received placebo matched to rhPTH (1-84) as SC injection QD with active vitamin D and calcium supplements up to 31.3 weeks.	rhPTH (1-84) n=45 participants at risk Participants received rhPTH (1-84) 50 mcg SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.
Psychiatric disorders Anxiety	2.1% 1/48 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).	0.00% 0/45 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).
Psychiatric disorders Bradyphrenia	0.00% 0/48 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).	2.2% 1/45 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ganglioneuroma	0.00% 0/48 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).	2.2% 1/45 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).
Infections and infestations Gastroenteritis	0.00% 0/48 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).	2.2% 1/45 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).
Metabolism and nutrition disorders Hypercalcaemia	4.2% 2/48 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).	0.00% 0/45 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).
Immune system disorders Hypersensitivity	0.00% 0/48 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).	2.2% 1/45 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).
Metabolism and nutrition disorders Hypocalcaemia	4.2% 2/48 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).	6.7% 3/45 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).
Infections and infestations Sinusitis	2.1% 1/48 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).	0.00% 0/45 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).
Metabolism and nutrition disorders Tetany	2.1% 1/48 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).	0.00% 0/45 • From start of study drug administration to 4 weeks post follow-up (up to Week 36) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Analysis Set included all participants in the ITT Set who took at least 1 dose of investigational product (study drug or placebo).

Other adverse events

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER