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A Clinical Study of rhPTH(1-84) Treatment in Japanese Participants With Chronic Hypoparathyroidism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03878953
Recruitment Status : Not yet recruiting
First Posted : March 18, 2019
Last Update Posted : May 7, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Shire )

Brief Summary:
This clinical study aims to evaluate the safety and efficacy of repeated dosing of recombinant human parathyroid hormone (rhPTH[1-84]) in Japanese participants with chronic hypoparathyroidism for a 26-week period.

Condition or disease Intervention/treatment Phase
Chronic Hypoparathyroidism Drug: rhPTH(1-84) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Open-label Clinical Study of rhPTH(1-84) Treatment in Japanese Subjects With Chronic Hypoparathyroidism
Estimated Study Start Date : March 31, 2022
Estimated Primary Completion Date : May 31, 2023
Estimated Study Completion Date : May 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: rhPTH(1-84)
Participants will receive a SC injection of initial dose of 50 mcg of rhPTH(1-84) once daily (QD) in the thigh (alternate thigh every day). If albumin-corrected serum calcium (ACSC; [mg/dL] = serum calcium [mg/dL] +0.8*[4-serum albumin (g/dL)]) is >2.25 mmol/L (>9.0 mg/dL), a starting dose of 25 mcg will be considered. At 4 week intervals the rhPTH(1-84) dose may be increased in 25 mcg increments to a maximal dose of 100 mcg SC QD. At any time during the study as needed for safety reasons, rhPTH(1-84) doses may be decreased in 25 mcg decrements to a minimum of 25 mcg QD. If the ACSC is >2.97 mmol/L (>11.9 mg/dL), then the investigational product should be stopped until the calcium level is corrected.
Drug: rhPTH(1-84)
Participants will receive a SC injection of initial dose of 50 mcg of rhPTH(1-84) once daily (QD) in the thigh (alternate thigh every day). If albumin-corrected serum calcium (ACSC; [mg/dL] = serum calcium [mg/dL] +0.8*[4-serum albumin (g/dL)]) is >2.25 mmol/L (>9.0 mg/dL), a starting dose of 25 mcg will be considered. At 4 week intervals the rhPTH(1-84) dose may be increased in 25 mcg increments to a maximal dose of 100 mcg SC QD. At any time during the study as needed for safety reasons, rhPTH(1-84) doses may be decreased in 25 mcg decrements to a minimum of 25 mcg QD. If the ACSC is >2.97 mmol/L (>11.9 mg/dL), then the investigational product should be stopped until the calcium level is corrected.




Primary Outcome Measures :
  1. Number of Responders at Week 26 [ Time Frame: Week 26 ]
    Number of participants who achieved an albumin-corrected total serum calcium concentration that is maintained or normalized compared to baseline and does not exceed the upper limit of the reference range for the laboratory, at least a 50% reduction from baseline amounts of active vitamin D therapy and at least a 50% reduction from the baseline oral calcium supplement dose (this criterion will be considered met if the participant's baseline calcium dose is <1000 mg and it does not increase during the study will be reported.

  2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From start of study treatment up to 30 weeks ]
    An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this study treatment. A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the investigational product or medicinal product.


Secondary Outcome Measures :
  1. Change From Baseline in Serum Phosphate Level [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 and 30 ]
    Change from baseline in serum phosphate level will be reported.

  2. Change From Baseline in Urine Calcium Level [ Time Frame: Baseline, Week 26 ]
    Change from baseline in urine calcium level will be reported.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The participant has signed and dated the informed consent form.
  • The participant is an adult male or female 20 to 85 years of age inclusive.
  • The participant is living in Japan and is Japanese; in this case, Japanese is defined as having been born in Japan, with Japanese parents, and Japanese maternal and paternal grandparents.
  • The participant has a diagnosis of chronic hypoparathyroidism with an onset of 18 months or more prior to screening. The diagnosis is based on historical biochemical evidence of hypocalcemia in the setting of a concomitant inappropriately low serum intact parathyroid hormone (PTH). If such evidence is not available the diagnosis of chronic hypoparathyroidism must be confirmed by the Shire medical monitor based on other compelling medical history.
  • The participant has been treated with active vitamin D therapy with alfacalcidol greater than or equal to (>=) 1 microgram (mcg) per day (or an equivalent dose of calcitriol of >=0.5 mcg per day or falecalcitriol >=0.3 mcg per day) prior to baseline.
  • The participant has indicated a willingness and ability to perform daily subcutaneous (SC) self-injections of study medication (or will have a designee, ie, a family member or caregiver, to perform injections).
  • Females of childbearing potential must agree to comply with the contraceptive requirements of the protocol.
  • The participants who are less than (<) 25 years old demonstrate radiological evidence of epiphyseal closure at screening based on bone age X-ray (single posteroanterior X-ray of the left wrist and hand).
  • The participant meets 1 of the following criteria:

    1. If not receiving thyroid hormone replacement therapy, the participant has a serum thyroid stimulating hormone (TSH) level within normal laboratory limits at screening.
    2. If receiving thyroid hormone replacement therapy, the dose must have been stable for at least 3 months prior to screening and serum TSH level within the reference range for the laboratory.
  • The participant has a 25-hydroxyvitamin D level >=50 nanomoles per litre (nmol/L) (20 nanogram per milliliter [ng/mL]) and < upper limit of normal (ULN) of the laboratory reference range.
  • The participant has a serum creatinine laboratory value of <132.6 micromoles per liter (mcmoles/L) (1.5 milligram per deciliter [mg/dL]).
  • The participant has a serum magnesium level within the laboratory reference range at baseline.
  • The participant is not adequately controlled with standard therapy within 6 months of screening based upon the opinion of the investigator and approval by the sponsor's medical monitor. For example:

    1. Hypocalcemia (albumin-corrected serum calcium <8.0 mg/dL) or
    2. Hypercalciuria (urine calcium [mg/dL]/creatinine [mg/dL] ratio >0.4 or 24 hour urine calcium excretion >7.5 millimoles (mmol) [300 milligram {mg}]/24 hours in men and >6.25 millimoles (mmol) [250 mg]/24 hours in women) or,
    3. Symptoms of hypoparathyroidism.

Exclusion Criteria:

  • The participant and/or legally authorized representative(s) is unable to understand the nature, scope, and possible consequences of the study.
  • The participant is unable to comply with the protocol, eg, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for evaluations, or is otherwise unlikely to complete the study, as determined by the investigator or the medical monitor.
  • The participant has any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as active hyperthyroidism, Paget's disease, type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (hemoglobin A1c [HbA1c] >8%), severe and chronic cardiac, liver or renal disease, Cushing's syndrome, neuromuscular disease, rheumatoid arthritis, myeloma, pancreatitis, malnutrition, rickets, recent prolonged immobility, active malignancy, primary or secondary hyperparathyroidism, a history of parathyroid carcinoma, hypopituitarism, acromegaly, or multiple endocrine neoplasia types I and II.
  • The participant has a known history of hypoparathyroidism resulting from an activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism).
  • The participant is taking prohibited medications (listed below) or other drugs known to influence calcium and bone metabolism during their respective prohibited periods.

    a) The following prohibited medications should not be taken within the specified number of days prior to the first dose of rhPTH(1-84): i) 30 days: loop diuretics, thiazide diuretics, phosphate binders (other than calcium carbonate), calcitonin, cinacalcet hydrochloride.

ii) 90 days: lithium. iii) 127 days: denosumab. iv) 180 days: digoxin, raloxifene hydrochloride, estrogens and progestins for hormone replacement therapy, methotrexate, systemic corticosteroids, oral bisphosphonates*.

v) 365 days: sodium fluoride, intravenous bisphosphonates*. Note: *The length of the washout period is dependent on the route of administration of bisphosphonate that is being used by the participant.

  • The participant has previous treatment or participation in an investigational trial with PTH-like drugs, including PTH(1-84), PTH(1-34) or other N terminal fragments or analogs of PTH or PTH-related protein within 6 months prior to screening.
  • The participant has nonhypocalcemic seizure disorder/epilepsy with a history of a seizure within the previous 6 months prior to screening; note that participant with a history of seizures due to hypocalcemia are allowed.
  • The participant has any disease or condition, in the opinion of the investigator, which has a high probability of precluding the participant from completing the study or that the participant cannot or will not appropriately comply with study requirements.
  • The participant has participated in any other investigational trial in which receipt of investigational drug or device occurred within 6 months prior to screening for this study.
  • The participant is pregnant or breastfeeding.
  • The participant has a history of diagnosed drug or alcohol dependence within the previous 3 years.
  • The participant has a history of gout.
  • The participant has disease processes that may adversely affect gastrointestinal absorption, including but not limited to short bowel syndrome, bowel resection, tropical sprue, celiac disease, ulcerative colitis, and Crohn's disease.
  • The participant has 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 pulse rate <50 beats/minute), or hypotension (systolic and diastolic blood pressures <100 and 60 millimeters of mercury (mmHg), respectively).
  • The participant has a history of cerebrovascular accident.
  • The participant has a known or suspected intolerance or hypersensitivity to the investigational product, PTH derivatives, or any of the stated ingredients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03878953


Contacts
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Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

Locations
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Japan
Fujita Health University Hospital
Toyoake-shi, Aichi-Ken, Japan, 470-1192
Contact: Site contact    81562932111    hibichan@fujita-hu.ac.jp   
Principal Investigator: Yatsuka Hibi         
University of Occupational and Environmental Health Japan
Kitakyushu-shi, Fukuoka-Ken, Japan, 807-8556
Contact: Site contact    81936031611    y-okada@med.uoeh-u.ac.jp   
Principal Investigator: Yosuke Okada         
Osaka City University Hospital
Osaka-shi, Osaka-Fu, Japan, 545-8586
Contact: Site contact    81666452121      
Principal Investigator: Yasuo Imanishi         
Shimane University Hospital
Izumo-shi, Shimane-Ken, Japan, 693-8501
Contact: Site contact    81853232111    tiken@med.shimane-u.ac.jp   
Principal Investigator: Mika Yamauchi         
Tokushima University Hospital
Tokushima-shi, Tokushima-Ken, Japan, 770-8503
Contact: Site contact    81886313111    endoits@tokushima-u.ac.jp   
Principal Investigator: Itsuro Endo         
University of Tokyo Hospital
Bunkyo-ku, Tokyo-To, Japan, 113-8655
Contact: Site contact    81338155411    nobitotky@gmail.com   
Principal Investigator: Nobuaki Ito         
The Cancer Institute Hospital of JFCR
Koto-ku, Tokyo-To, Japan, 135-8550
Contact: Site Contact    '+81335200111    konosuke.nakayama@jfcr.or.jp   
Principal Investigator: Konosuke Nakayama         
Toranomon Hospital
Minato-ku, Tokyo-To, Japan, 105-8470
Contact: Site contact    81335881111    takeuchi-tky@umin.ac.jp   
Principal Investigator: Yasuhiro Takeuchi         
Keio University Hospital
Shinjuku-ku, Tokyo-To, Japan, 160-8582
Contact: Site contact    +81333531211    i-kuri@dc4.so-net.ne.jp   
Principal Investigator: Isao Kurihara         
Tokyo Women's Medical University Hospital
Shinjuku-ku, Tokyo-To, Japan, 162-8666
Contact: Site contact    81333538111    okamoto.takahiro@twmu.ac.jp   
Principal Investigator: Takahiro Okamoto         
Sponsors and Collaborators
Shire
Investigators
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Study Director: Study Director Shire
Additional Information:
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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03878953    
Other Study ID Numbers: SHP634-301
194828 ( Registry Identifier: JapicCTI )
First Posted: March 18, 2019    Key Record Dates
Last Update Posted: May 7, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. 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://vivli.org/ourmember/takeda/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Hypoparathyroidism
Parathyroid Diseases
Endocrine System Diseases