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)]
- Conditions
- Insufficient thyroid function10052547
- Registration Number
- NL-OMON55679
- Lead Sponsor
- Shire Human Genetic Therapies, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
1. Has an understanding, ability, and willingness to fully comply with study
procedures and restrictions.
2. Is able to voluntarily provide a signed and dated informed consent form
before any study-related procedures are performed.
3. Is an adult male or female 18 to 85 years of age, inclusive.
4. In subjects 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)
5. 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., 6. During
the Week -3 screening visit, the subject 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)., 7. The subject must have a Hypoparathyroidism Symptom
Diary (HPT-SD) symptom subscale Sum Score of >=10 during the 14-day period
immediately prior to the baseline (Week 0) visit (Day -14 to Day -1). In
addition, the subject 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. See Appendix 3 for the calculation of the sum score., 8. 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.
• The subject must be taking >=0.5 µg/day of calcitriol or >=1.0 µg/day of
alfacalcidol.
• If the subject is treated with a lower dose of active vitamin D the subject
must also be taking calcium supplements of at least 800 mg/day of elemental
calcium, 9. Has thyroid-stimulating hormone (TSH) results within normal
laboratory limits at screening for all subjects not receiving thyroid hormone
replacement therapy. For subjects 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 the normal
range. A serum TSH level below the lower limit of the normal range but not
undetectable in subjects treated with thyroid hormone may be allowed if there
is no anticipated need for a change in thyroid hormone dose during the trial.,
10. Has serum 25-hydroxyvitamin D levels >=50 nmol/L (20 ng/mL) and <1.5
times the upper limit of normal (ULN) for the central laboratory normal range.,
11. Has estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2., 12.
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., 13. 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., 14. With regard to female subjects:
women who are postmenopausal (12 consecutive months of spontaneous amenorrhea
and age more than or equal to 51 years) and women who are surgically sterilized
can be enrolled. Wo
1. History of hypoparathyroidism resulting from a known activating mutation in
the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism)., 2.
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.
3. 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.
4. If the Blood calcium level is above the ULN at the baseline (Week 0) visit,
the analysis can be repeated another day as long as the next date is within the
visit window for the baseline visit. If the subject does not met exclusion #4
on the repeat measure the subject may be randomized., 5. 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. See Section 5 (Prior and
Concomitant Treatment) for a list of prohibited and restricted medications, 6.
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., 7. Use of other drugs known to
influence calcium and bone metabolism, such as calcitonin, fluoride tablets, or
cinacalcet hydrochloride, within the prohibited period., 8. Use of oral
bisphosphonates within the previous 6 months or intravenous bisphosphonate,
preparations within the previous 24 months before screening., 9.
Nonhypocalcemic seizure disorder with a history of a seizure within the
previous 6 months before screening. Subjects with a history of seizures that
occur in the setting of hypocalcemia are allowed., 10. The subject 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., 11. Any disease or condition
that, in the opinion of the investigator, may require treatment or make the
subject 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., 12. Pregnant or lactating
women., 13. Known or suspected intolerance o
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective is to test the hypothesis that rhPTH(1-84) treatment can<br /><br>result in superior improvements in the symptoms of hypoparathyroidism as<br /><br>assessed by the Hypoparathyroidism Symptom Diary (HPT-SD) symptom subscale<br /><br>compared with standard therapy.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The key secondary objectives are to test the hypotheses that rhPTH(1-84)<br /><br>treatment can result in superior improvements in:<br /><br>- Fatigue as assessed by the Functional Assessment of Chronic Illness<br /><br>Therapy-Fatigue (FACIT-Fatigue) compared with standard therapy.<br /><br>- The physical component summary (PCS) derived from the 36-Item Short Form<br /><br>Health Survey version 2 (SF-36v2) acute version compared with standard therapy.</p><br>