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Study of the Effect of Recombinant Human Parathyroid Hormone [rhPTH(1-84)] on Symptoms Improvement and Metabolic Control Among Adults With Hypoparathyroidism

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ClinicalTrials.gov Identifier: NCT03324880
Recruitment Status : Recruiting
First Posted : October 30, 2017
Last Update Posted : April 15, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

Tracking Information
First Submitted Date  ICMJE October 10, 2017
First Posted Date  ICMJE October 30, 2017
Last Update Posted Date April 15, 2019
Actual Study Start Date  ICMJE February 15, 2018
Estimated Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2018)
Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Subscale Score at Week 26 [ Time Frame: Baseline, Week 26 ]
The HPT-SD is 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 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. For symptom subscale score, the average score of the symptom items 1-7 will be calculated.
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2017)
Change in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Subscale Score From Baseline to Week 26 [ Time Frame: Baseline, Week 26 ]
Change in HPT-SD symptom subscale score from baseline to Week 26 will be reported.
Change History Complete list of historical versions of study NCT03324880 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2018)
  • Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    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 4-point Likert scale. Thus, the total score ranges from 0 to 52. High scores represent less fatigue.
  • Change From Baseline in Physical Component Summary (PCS) Derived From 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores at Week 26 [ Time Frame: Baseline, Week 26 ]
    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 PCS derived from SF-36v2 at Week 26 will be reported.
  • Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Impact Subscale Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    The HPT-SD is 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 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. For Impact subscale, the average score of the impact items 10-13 will be calculated.
  • Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HPT-SD) Impact Items Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    The HPT-SD is 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 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2.
  • Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Item Anxiety (item 8) Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    The HPT-SD is 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 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2.
  • Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Item Sadness or Depression (Item 9) Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    The HPT-SD is 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 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2.
  • Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Items Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    The HPT-SD is 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 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. The change in individual symptom item scores will be reported.
  • Number of Participants With Response at Week 26 [ Time Frame: Baseline to Week 26 ]
    Response is defined as a 30% reduction in HPT-SD symptom subscale score from baseline. The HPT-SD is 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 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. For symptom subscale score, the average score of the symptom items 1-7 will be calculated.
  • Change From Baseline in the Most Bothersome Symptom Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    The HPT-SD is 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 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. The Most Bothersome Symptom Score will be analyzed.
  • Change From Baseline in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) assessment is a 37-item instrument. Each item will be scored from 0=Not at all to 4=Very much.
  • Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 [ Time Frame: Baseline, Week 26 ]
    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 will be reported.
  • Change From Baseline in Mental Component Summary (MCS) Score of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 [ Time Frame: Baseline, Week 26 ]
    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 will be reported.
  • Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Hypoparathyroidism (WPAI:Hypoparathyroidism) Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    The WPAI:Hypoparathyroidism will be used to assess how hypoparathyroidism affects partcipants' ability to work and perform regular activities. Concepts that the WPAI:Hypoparathyroidism measures include time missed from work and impairment of work and other regular activities due to specific health problems. The change from baseline in the questionnaire response will be reported.
  • Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Severity (PGI-S) at Week 26 [ Time Frame: Baseline, Week 26 ]
    The PGI-S is a verbal rating scale asks the respondent to best describe how their symptoms severity. Response options are no symptoms, mild, moderate, severe and very severe. Mean change in scores of PGI-S at Week 26 will be reported.
  • Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Change (PGI-C) at Week 26 [ Time Frame: Baseline, Week 26 ]
    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 very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse. Mean change in scores of PGI-C at Week 26 will be reported.
  • Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 [ Time Frame: Baseline, Week 24 ]
    The neurocognitive test battery will include tests evaluating the frontal-executive domain, which encompasses functions attributable to the prefrontal cortex and its connections to the basal ganglia (mostly striatum). The tests will include 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 will be reported.
  • Change From Baseline in At-Home Neurocognitive Assessment Scores at Week 24 [ Time Frame: Baseline, Week 24 ]
    The neurocognitive test battery will include tests evaluating the frontal-executive domain, which encompasses functions attributable to the prefrontal cortex and its connections to the basal ganglia (mostly striatum). The tests will include 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). Changes in at-home neurocognitive assessment scores (CS Brief Battery) at Week 24 will be reported.
  • Change From Baseline in 24-hour Urine Calcium Excretion at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in 24-hour urine calcium excretion at Week 26 will be reported.
  • Change From Baseline in Serum Phosphate Level at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in serum phosphate level at Week 26 will be reported.
  • Change From Baseline in Doses of Active Vitamin D and Calcium Supplements at Week 26 [ Time Frame: Baseline, Week 26 ]
    Changes in doses of active vitamin D and calcium supplements at Week 26 will be reported.
  • Number of Participants With Albumin-corrected Serum Calcium Control at Week 26 [ Time Frame: Week 26 ]
    Number of participants with albumin-corrected serum calcium between 1.875 millimoles per liter (mmol/L) (7.5 milligram per decilitre [mg/dL]) and upper limit of normal (ULN) for the central laboratory normal range at Week 26 will be reported.
  • Number of Participants who Achieve Composite Criteria for Albumin-corrected Serum Calcium Concentration, Vitamin D Dose and Oral Calcium Supplement Dose at Week 26 [ Time Frame: Baseline to Week 26 ]
    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 calcium supplement dose at Week 26 will be reported.
  • Change From Baseline in Bone Turnover Markers at Week 26 [ Time Frame: Baseline, Week 26 ]
    Bone turnover markers includes serum bone-specific alkaline phosphatase, procollagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From start of study drug administration up to Week 30 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2017)
  • Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in FACIT-fatigue score at Week 26 will be reported.
  • Change in Physical Component Summary (PCS) Derived From 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in PCS derived from SF-36v2 at Week 26 will be reported.
  • Percentage of Participants Achieving Minimal Clinical Important Difference (MCID) in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Subscale Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    Percentage of participants achieving MCID in HPT-SD symptom subscale score at Week 26 will be reported.
  • Change in Hypoparathyroidism Symptom Diary (HPT-SD) Impact Subscale Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in the impact subscale score at Week 26 will be reported.
  • Change in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Item Anxiety (item 8) and Symptom Item Sadness or Depression (Item 9) Individual Item Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in the HPT-SD symptom item anxiety (item 8) and symptom item sadness or depression at Week 26 will be reported.
  • Change in Individual Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Items Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in score of individual HPT-SD symptom items at Week 26 will be reported.
  • Change in Individual Hypoparathyroidism Symptom Diary (HPT-SD) Impact Items Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in score of individual HPT-SD impact items at Week 26 will be reported.
  • Change in Individual Domains and Mental Component Summary (MCS) Score of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in the score of individual domains and MCS of SF-36v2 at Week 26 will be reported.
  • Change in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in FACT-Cog score at Week 26 will be reported.
  • Change in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in WPAI-SHP score at Week 26 will be reported.
  • Change in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Severity (PGI-S) at Week 26 [ Time Frame: Baseline, Week 26 ]
    Mean change in scores of PGI-S at Week 26 will be reported.
  • Change in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Change (PGI-C) at Week 26 [ Time Frame: Baseline, Week 26 ]
    Mean change in scores of PGI-C at Week 26 will be reported.
  • Change in In-Clinic Neurocognitive Assessment Scores at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in in-clinic neurocognitive assessment scores at Week 24 will be reported.
  • Change in At-Home Neurocognitive Assessment Scores at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in at-home neurocognitive assessment scores (cogstate brief battery) at Week 26 will be reported.
  • Change in 24-hour Urine Calcium Excretion at Week 26 [ Time Frame: Baseline, Week 26 ]
    Effect of rhPTH(1-84) on change in 24-hour urine calcium excretion at Week 26 will be reported.
  • Number of Participants With Albumin-corrected Serum Calcium Concentration at Week 26 [ Time Frame: Baseline, Week 26 ]
    Number of participants with albumin-corrected serum calcium between 1.875 millimolar per liter (mmol/L) (7.5 milligram per decilitre [mg/dL]) and upper limit of normal (ULN) for the central laboratory normal range at Week 26 will be reported.
  • Number of Participants With Change in Serum Phosphate Level at Week 26 [ Time Frame: Baseline, Week 26 ]
    Number of participants with change in serum phosphate level at Week 26 will be reported.
  • Change in Doses of Active Vitamin D and Calcium Supplements at Week 26 [ Time Frame: Baseline, Week 26 ]
    Changes in doses of active vitamin D and calcium supplements will be reported at Week 26.
  • Number of Participants Achieving Albumin-corrected Serum at Week 26 [ Time Frame: Week 26 ]
    Number of participants achieving albumin-corrected serum calcium between 1.875 mmol/L (7.5 mg/dL) and the ULN for the central laboratory normal range at Week 26 will be reported.
  • Number of Participants Achieving 50 Percent (%) Decrease in Dose of Active Vitamin D at Week 26 [ Time Frame: Week 26 ]
    Number of participants achieving 50 percent (%) decrease in dose of active vitamin D at Week 26 will be reported.
  • Number of Participants Achieving 50 percent (%) or More Decrease in Dose of Oral Calcium Supplement at Week 26 [ Time Frame: Week 26 ]
    Number of participants achieving 50 % or more decrease in dose of oral calcium supplement at Week 26 will be reported.
  • Markers of Bone Turnover at Week 26 [ Time Frame: Week 26 ]
    Bone turnover markers includes serum bone-specific alkaline phosphatase, procollagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin. Markers of bone turnover at Week 26 will be reported.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From start of study drug administration up to Week 30 ]
    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.
  • Number of Participants With Hypocalcemic Adverse Events (AEs) [ Time Frame: From start of study drug administration up to Week 30 ]
    Hypocalcemia AEs reported in the study are categorized into severe hypocalcemia, self-treated hypocalcemia, and mild to moderate hypocalcemia that are not self-treated.
  • Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event [ Time Frame: From start of study drug administration up to Week 30 ]
    Vital sign assessments include blood pressure, pulse, body temperature, and respiratory rate.
  • Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event [ Time Frame: From start of study drug administration up to Week 30 ]
    Clinical laboratory evaluations include serum chemistry, hematology, and urinalysis.
  • Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event [ Time Frame: From start of study drug administration up to Week 30 ]
    12-lead ECG will be recorded and measured with the participant in rested supine position for at least 5 minutes.
  • Number of Participants With Antiparathyroid Hormone (PTH) Antibodies [ Time Frame: Baseline, Week 12, Week 30 ]
    Number of participants with positive Anti-PTH antibodies will be reported.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Effect of Recombinant Human Parathyroid Hormone [rhPTH(1-84)] on Symptoms Improvement and Metabolic Control Among Adults With Hypoparathyroidism
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Adaptive Study to Evaluate Symptom Improvement and Metabolic Control Among Adult Subjects With Symptomatic Hypoparathyroidism Treated With Recombinant Human Parathyroid Hormone [rhPTH(1-84)]
Brief Summary The purpose of this study is to evaluate whether adding an investigational medication called recombinant human parathyroid hormone (rhPTH[1-84]) to standard hypoparathyroidism therapy (oral calcium and active vitamin D tablets) may result in superior improvements in symptoms of hypoparathyroidism assessed by hypoparathyroidism symptom diary (HPT-SD) symptom scale compared with standard therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hypoparathyroidism
Intervention  ICMJE
  • Biological: rhPTH(1-84)
    rhPTH(1-84) 25, 50, 75, and 100 mcg QD SC injection will be administered
  • Biological: Placebo
    Placebo QD SC injection will be administered
Study Arms  ICMJE
  • Experimental: rhPTH(1-84)
    Participants will receive rhPTH(1-84) 50 microgram (mcg) subcutaneous (SC) injection once daily (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.
    Intervention: Biological: rhPTH(1-84)
  • Placebo Comparator: Placebo
    Participants will receive placebo matched to rhPTH(1-84) as SC injection QD with active vitamin D and calcium supplements.
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 24, 2017)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 25, 2020
Estimated Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has an understanding, ability, and willingness to fully comply with study procedures and restrictions.
  • Is able to voluntarily provide a signed and dated informed consent form before any study-related procedures are performed.
  • Is an adult male or female 18 to 85 years of age, inclusive.
  • In participants 18-25 years of age, has radiological evidence of epiphyseal closure based on bone age X-ray (single posteroanterior X-ray of left wrist and hand) before randomization.
  • Has chronic hypoparathyroidism with onset 12 months or more before screening. The diagnosis of hypoparathyroidism is established based on hypocalcemia in the setting of inappropriately low serum PTH levels.
  • During the Week -3 screening visit, the participant reports by history at least 2 of the following symptoms related to hypoparathyroidism occurring within the 2 weeks before Week -3 visit: muscle cramps, muscle spasms or twitching, tingling, numbness, heaviness in arms or legs, physical fatigue, or slowed or confused thinking (brain fog).
  • The participant must have a Hypoparathyroidism Symptom Diary (HPT-SD) symptom subscale Sum Score of greater than or equal to (>=) 10 during the 14-day period immediately prior to the baseline (Week 0) visit (Day -14 to Day -1). In addition, the participant must have at least 4 HPT-SD diaries completed in the first 7 day period and at least 4 HPT-SD diaries completed in second 7 day period.
  • Must be treated with active vitamin D (calcitriol or alfacalcidol) alone or in conjunction with calcium supplements for at least 4 months prior to the screening visit.

    1. The participant must be taking >= 0.5 microgram (μg)/day of calcitriol or >=1.0 μg/day of alfacalcidol.
    2. If the participant is treated with a lower dose of active vitamin D the participant must also be taking calcium supplements of at least 800 milligrams per day (mg/day) of elemental calcium.
  • Has serum thyroid-stimulating hormone (TSH) results within normal laboratory limits at screening for all participants not receiving thyroid hormone replacement therapy. For participants on thyroid hormone replacement therapy, the thyroid hormone dose must have been stable for at least 4 weeks before screening, and serum TSH level must be within the central laboratory normal range. A serum TSH level below the lower limit of the normal range but not undetectable in participant treated with thyroid hormone may be allowed if there is no anticipated need for a change in thyroid hormone dose during the trial.
  • Has serum 25-hydroxyvitamin D levels >=50 mmol/L (20 nanograms per milliliter [ng/mL]) and less than (<) 1.5 times the upper limit of normal (ULN) for the central laboratory normal range.
  • Has estimated glomerular filtration rate (eGFR) greater than (>) 30 milliliter per minute per 1.73 square meters (ml/min/1.73m^2).
  • Prior to randomization, is able to perform daily SC self-injections of study medication (or have a designee perform injection) via a multidose injection pen into the thigh.
  • Willing to use oral active vitamin D and calcium supplements provided for the study unless directed to remain on the supplements used prior to enrollment in the current study by the investigator after consultation with the medical monitor.
  • With regard to female participants: women who are postmenopausal (12 consecutive months of spontaneous amenorrhea and age >= 51 years) and women who are surgically sterilized can be enrolled. Women of childbearing potential must have a negative pregnancy test at randomization and be willing to comply with any applicable contraceptive requirements of the protocol and pregnancy testing for the duration of the study.

Exclusion Criteria:

  • History of hypoparathyroidism resulting from a known activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism).
  • Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as poorly controlled hyperthyroidism; Paget disease; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus; severe and chronic cardiac, liver (Child-Pugh score >9) (US FDA, 2003), or renal disease; Cushing syndrome; rheumatoid arthritis; myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer); primary or secondary hyperparathyroidism; or documented parathyroid carcinoma within the previous 5 years, acromegaly, or multiple endocrine neoplasia types 1 and 2.
  • Very low or very high blood calcium level (eg, ACSC <1.87 mmol/L [<7.5 mg/dL] or >=2.97 mmol/L [>=11.9 mg/dL]) at the Week -3 screening visit. Results from the central laboratory must be used for this assessment.
  • Blood calcium level above the ULN at the baseline (Week 0) visit. Results from a local laboratory may be used for this assessment.
  • Use of prohibited medications, such as loop and thiazide diuretics, phosphate binders (other than calcium carbonate), digoxin, lithium, methotrexate, or systemic corticosteroids, within respective prohibited periods.
  • Participation in any other investigational study in which receipt of investigational drug or device occurred within 6 months before screening for this study. Prior treatment with PTH-like drugs (whether commercially available or through participation in an investigational study), including PTH(1-84), PTH(1-34), or other N-terminal fragments or analogs of PTH or PTH-related protein, within 3 months before screening.
  • Use of other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets, or cinacalcet hydrochloride, within the prohibited period.
  • Use of oral bisphosphonates within the previous 6 months or intravenous bisphosphonate preparations within the previous 24 months before screening.
  • Nonhypocalcemic seizure disorder with a history of a seizure within the previous 6 months before screening. Participants with a history of seizures that occur in the setting of hypocalcemia are allowed.
  • The participant is at increased baseline risk for osteosarcoma, such as those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, hereditary disorders predisposing to osteosarcoma, or with a prior history of external beam or implant radiation therapy involving the skeleton.
  • Any disease or condition that, in the opinion of the investigator, may require treatment or make the participant unlikely to fully complete the study or any condition that presents undue risk from the investigational product or procedures. For example, illness that is anticipated to be chronic and not transient.
  • Pregnant or lactating women.
  • Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients.
  • History of diagnosed drug or alcohol dependence within the previous 3 years.
  • Poorly controlled short bowel syndrome, bowel resection, tropical sprue, celiac disease, ulcerative colitis, and Crohn disease.
  • Chronic or severe cardiac disease including but not limited to heart failure (according to the New York Heart Association classification Class II to Class IV) (Dolgin and NYHA, 1994), arrhythmias, bradycardia (resting heart rate <50 beats/minute).
  • History of cerebrovascular accident.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com
Listed Location Countries  ICMJE Belgium,   Denmark,   France,   Germany,   Italy,   Netherlands,   Norway,   Portugal,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03324880
Other Study ID Numbers  ICMJE SHP634-401
2017-000284-32 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers
Responsible Party Shire
Study Sponsor  ICMJE Shire
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Shire
PRS Account Shire
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP