Oral PTH(1-34) PK and PD Study in Patients With Hypoparathyroidism

NCT03516773 | Completed Phase 2

• 1 other identifier: ENT-04-2018
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

A Randomized, active comparator, two-part, partial crossover design. The study is designed to assess the pharmacokinetics and pharmacodynamics of EnteraBio's Oral PTH(1-34) \[EB612 (EBP05)\] in adult patients with hypoparathyroidism.

Conditions

Hypoparathyroidism

Keywords

Hypoparathyroidism, PTH(1-34), Parathyroid Hormone

Outcome Measures

Primary Outcomes (3)

• Plasma PTH(1-34) levels

  Pharmacokinetic Parameter

  18 weeks

• Serum albumin-adjusted total calcium levels

  Pharmacodynamic Parameter

  18 weeks

• urinary calcium levels

  Pharmacodynamic Parameter

  18 weeks

Secondary Outcomes (2)

• Adverse Events

  60 days

• Rate of Adverse Events leading to discontinuation

  60 days

Study Arms (5)

Treatment A

EXPERIMENTAL

Intervention: EB612 (EBP05) 2.25 mg orally (PO) four times a day (QID) (approximately 5 hours apart) for 4 doses, for a total dose of 9 mg per day

Drug: EB612 (EBP05)

Treatment B

EXPERIMENTAL

Intervention: EB612 (EBP05) 2.25 mg PO twice a day (BID) (approximately 10 hours apart) for 2 doses, for a total dose of 4.5 mg per day

Drug: EB612 (EBP05)

Treatment C

ACTIVE COMPARATOR

Intervention: NATPARA/NATPAR PTH(1-84) 100 μg subcutaneous injection once daily (single dose)

Drug: NATPARA/NATPAR

Treatment D

EXPERIMENTAL

Intervention: EB612 (EBP05) 2.25 mg PO TID (dose 1 and dose 2 approximately 10 hours apart; dose 2 and dose 3 approximately 5 hours apart- TID schedule option 2), for a total dose of 6.75 mg per day

Drug: EB612 (EBP05)

Treatment E - EB612 (EBP05)

EXPERIMENTAL

Intervention: EB612 (EBP05) 0.75 mg PO TID (dose 1 and dose 2 approximately 10 hours apart; dose 2 and dose 3 approximately 5 hours apart- TID schedule option 2), for a total dose of 2.25 mg per day

Drug: EB612 (EBP05)

Interventions

EB612 (EBP05) DRUG

Entera Bio's proprietary drug for the administration of PTH(1-34) orally

Also known as: Oral PTH(1-34)

Treatment A; Treatment B; Treatment D; Treatment E - EB612 (EBP05)

NATPARA/NATPAR DRUG

A PTH replacement (PTH \[1-84\]; NATPARA (Shire-NPS Pharmaceuticals, Inc., Lexington, Massachusetts) was approved by the United States (US) Food and Drug Administration (FDA) in April 2015 / NATPAR (Shire Pharmaceuticals Ltd., Dublin, Ireland) was approved by the European Medicines Agency in April 2017 for use as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. Like many other hormonally active peptides, PTH (1 84); NATPARA is parenterally administered. In this protocol when a specific formulation is referenced (e.g. NATPARA) it may be read interchanged with the alternate formulation (e.g. NATPAR).

Also known as: PTH(1-84)

Treatment C

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of primary hypoparathyroidism, as defined by the European Society of Endocrinology as a patient with hypocalcemia and inappropriately low PTH levels. If the source of hypoparathyroidism is surgical or iatrogenic, diagnosis must be for more than 1 year. If the source of hypoparathyroidism is not surgical or iatrogenic, and confirmed by inappropriately low PTH levels and hypercalciuria, diagnosis does not have time limitations.
• , 25(OH)2D levels ≥20 ng/mL.
• Signed Informed Consent Form).
• Age 18 to 80 years with body mass index of 19 to 35 kg/m2.
• Patients able to adhere to the visit schedule and protocol requirements.

You may not qualify if:

• Known history of hypoparathyroidism resulting from an activating mutation in the calcium sensing receptor gene or impaired responsiveness to PTH (pseudohypoparathyroidism).
• Hemoglobin \<11.5 g/dL (females) / \<12.5g/dL (males) \[lower limit of reference range, 12 to 15 g/dL and 13 to 17 g/dL\]
• Acute or chronic renal failure (estimated glomerular filtration rate \<60 mL/min/1.73 m²).
• Significant liver function impairment (liver enzymes above ×2 the upper limit of normal range).
• Patients with hypomagnesemia should be excluded unless serum magnesium is corrected prior to study initiation.
• Active gastrointestinal inflammatory, gastrointestinal motility disorders, and chronic gastritis, such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, short bowel syndrome, celiac disease, gastroparesis, etc.
• Active hepatitis or acquired immunodeficiency syndrome (AIDS)/AIDS-related syndrome
• Any conditions or factors that, in the judgment of the Investigator, somehow may impact gastrointestinal absorption.
• Concurrent therapy with the following medications: (1) 14 days: thiazide diuretics; loop diuretics (2) 30 days: lithium, systemic corticosteroid; (3) 1 month: calcitonin, cinacalcet hydrochloride, recombinant PTH(1-84) or N-terminal PTH or PTH-related peptide fragments or analogs; (4) females only; changes in hormone replacement therapy within 2 months; (5) 3 months: methotrexate, growth hormone, digoxin; raloxifene or similar selective estrogen receptor modulators; (7) chronic or concurrent use of gastrointestinal motility modulators (domperidone, loperamide, erythromycin metoclopramide etc.); and (8) other concurrent therapy that, in the Investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study medication.
• Significant drug or alcohol abuse as assessed by the PI.
• Treatment with any investigational product within the last 30 days or 5 half-lives (if known) whichever is longer.
• Has participated as a patient in any investigational drug study within the last 30 days preceding the screening visit or plans to participate in another investigational drug study at any time during the study or within 30 days of his/her completion of this study.
• Presence of any other condition or circumstance that, in the judgment of the Investigator, might increase the risk to the patient or decrease the chance of obtaining satisfactory data to achieve the objectives of the study.
• Historical documented allergy to soy bean products or known hypersensitivity to the PTH (1-34).
• Patients at increased 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 involving the skeleton.

Sponsors & Collaborators

• Entera Bio Ltd.: lead

Study Sites (1)

Clinical Research Center Hadassah Ein Kerem Medical Center

Jerusalem, 91120,, Israel

Location

MeSH Terms

Conditions

Hypoparathyroidism

Interventions

Parathyroid Hormone

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Arthur Santora, MD

  Entera Bio Ltd.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, active comparator, two-part, within-part, partial crossover design.

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 4, 2018
• Study Start: June 17, 2018
• Primary Completion: December 5, 2018
• Study Completion: February 24, 2019
• Last Updated: March 26, 2019

Record last verified: 2019-03

Locations

IL (1)