Clinical trial NCT05965167: Assess Safety and Compare PK of New Oral hPTH(1-34) Tablet Formulations vs. EBP05 Tablets and Subcutaneous Forteo
Official title: A Phase 1b, Open-label, Partially Randomised Study to Assess Safety and Compare Pharmacokinetics of New Oral hPTH(1-34) Tablet Formulations vs. Oral EBP05 Tablets and Subcutaneous Forteo® Injection in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hypoparathyroidism
Osteoporosis
Fractures, Bone
Other Disease
Keywords: Hypoparathyroidism
PTH(1-34)
Parathyroid Hormone
Teriparatide
Osteoporosis
Lead sponsor: Entera Bio Ltd.
Sponsor class: INDUSTRY
First posted: 2023-07-28
Enrollment: 45
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to characterize and compare the pharmacokinetics of hPTH(1 34) after treatment with a modified oral formulation (EBP11 and EBP22) versus two dose levels of Entera Bio's extensively studied oral EBP05 1.5 mg and 2.5 mg as well as the commercial Forteo 0.02 mg subcutaneous injection.


Eligibility criteria: Inclusion Criteria:

1. Healthy male subjects, 18 - 35 years of age, inclusive, at screening.
2. Continuous nonsmoker who has not used nicotine containing products (including e-cigarettes, vapors, etc.) for at least 12 months prior to first dosing and throughout the study, based on subject self-reporting.
3. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening.
4. Medically healthy with no clinically significant medical condition, physical examination, laboratory profiles, vital signs, orthostatic vital sign measurements, or ECGs, as deemed by the PI or designee to be relevant to the study and does not pose an additional risk to the subject by their participation in the study.
5. Understands the study procedures described in the Informed Consent Form (ICF), be willing and able to comply with the protocol, and provides written consent.

Exclusion Criteria:

1. History or current condition of mental instability or cognitive impairment that, in the opinion of the investigator, could compromise the validity of informed consent, compromise the safety of the participant, or lead to nonadherence with the study protocol or inability to conduct the study procedures.
2. Active gastrointestinal inflammatory disorder, gastrointestinal motility disorders, and chronic gastritis, including but not limited to: ulcerative colitis, Crohn's disease, irritable bowel syndrome, short bowel syndrome, celiac disease, gastroparesis, that may affect drug bioavailability.
3. Any conditions or factors that, in the judgment of the PI or designee, somehow may impact gastrointestinal absorption, distribution or metabolism of parathyroid hormone analogues, or known to potentiate or predispose to undesired effects.
4. History of significant gastrointestinal, liver or kidney disease, or gastrointestinal surgery (including bariatric surgery, or any other interventional procedures with stomach and intestinal tract) that may affect either drug bioavailability, or hPTH(1-34) or SNAC metabolism.
5. History or presence of alcohol or drug abuse or positive urine drug or blood alcohol results at screening.
6. Known allergies or sensitivities to components of the Study Medication (e.g. soy) or known hypersensitivity to PTH or hPTH(1-34).
7. History or presence of clinically significant:

   * Urolithiasis;
   * Angina at Screening, in the opinion of the PI;
   * Hypocalcemia or hypercalcemia at screening;
   * Personal or family history of congenital long QT syndrome or known family history of sudden death.
8. Subjects with ECG findings deemed abnormal with clinical significance by the PI or designee at screening for the following:

   * QTcF interval \> 470 msec;
   * PR \> 220 msec;
   * QRS \> 120 msec.
9. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
10. Seated blood pressure is less than 90 systolic or 40 diastolic mmHg or greater than 140 systolic or 90 diastolic mmHg at screening;
11. Orthostatic vital sign results with a decrease in systolic \> 20 mmHg or decrease in diastolic \> 10 mm Hg, and/or increase in heart rate of \> 20 beats per minute at screening or Day 1 check-in.
12. Seated heart rate is lower than 50 bpm or higher than 99 bpm at screening (when clinically significant as determined by PI).
13. Estimated creatinine clearance \< 80 mL/min at screening
14. Unable to refrain from or anticipates the use of:

    * Any drug, including prescription and nonprescription medications, herbal remedies, or vitamin supplements that should be taken on the treatment visit day before the dosing of Study Medication and 2 hours after the dosing of Study Medication.
    * H2 blocker or PPI or antacid (including prescription and nonprescription) three days before the dosing of the Study Medication and 2 hours after the dosing of Study Medication.
15. Donation of blood or significant blood loss within 56 days prior to first dosing.
16. Hemoglobin levels below 13 g/dL at screening or at in screening test done during the study.
17. Plasma donation within 7 days prior to first dosing.
18. Participation in another interventional clinical study within 30 days prior to screening visit.

Primary outcomes:
measure: Assessment of the pharmacokinetic profile of plasma hPTH(1-34) after single or twice daily oral administration for treatment regimen as listed under Arms and Interventions at 5, 10, 15, 20, 40, 50, 60, 75, 90, 105, 120, 180, 240, 360 min. post dose
timeFrame: 6 hours
measure: Calculation of plasma levels of hPTH(1-34) AUC0-t for each treatment regimen
timeFrame: 6 hours
measure: Calculation of plasma levels of hPTH(1-34) AUC0-inf for each treatment regimen
timeFrame: 6-14 hours
measure: Calculation of plasma levels of hPTH(1-34) AUC%extrap for each treatment regimen
timeFrame: 6-14 hours
measure: Calculation of plasma levels of hPTH(1-34) Cmax for each treatment regimen
timeFrame: 6-14 hours
measure: Calculation of plasma levels of hPTH(1-34) Tmax for each treatment regimen
timeFrame: 6-14 hours
measure: Calculation of plasma levels of hPTH(1-34) Kel for each treatment regimen
timeFrame: 6 hours
measure: Calculation of plasma levels of hPTH(1-34) t½ for each treatment regimen
timeFrame: 6-14 hours
measure: Calculation of plasma levels of hPTH(1-34) Tlast for each treatment regimen
timeFrame: 6-14 hours
measure: Assessment of inter-subject variability of hPTH(1-34) for each treatment regimen
timeFrame: 6-14 hours
measure: Calculation of dose proportionality for hPTH(1-34) for relevant treatment regimen
timeFrame: 6 hours
measure: Assessment of the duration of exposure to hPTH(1-34) in minutes
timeFrame: 6 hours
measure: Vital Signs - body temperature (Celsius)
timeFrame: 6 hours
measure: Vital Signs - respiratory rate (breaths per minute)
timeFrame: 6 hours
measure: Vital Signs - blood pressure (systolic/diastolic mmHg)
timeFrame: 6 hours
measure: Vital Signs - heart rate (beats per minute)
timeFrame: 6 hours
measure: Incidence of Treatment-Emergent Adverse Events as assessed by the Principle Investigator
timeFrame: 6-14 hours
measure: Incidence of Serious Adverse Events (SAEs) as assessed by the Principle Investigator
timeFrame: 6-14 hours
Secondary outcomes:
Other outcomes:
measure: Measurement of plasma soybean trypsin inhibitor, Kunitz type (SBTI) levels (EBP05 only)
timeFrame: 6 hours
measure: Measurement of plasma salcaprozate sodium (SNAC) levels (EBP05 only)
timeFrame: 6 hours
measure: Measurement of serum calcium (albumin-corrected total calcium) for all treatment regimen
timeFrame: 6 hours
measure: Measurement of serum phosphate for all treatment regimen
timeFrame: 6 hours
measure: Measurement of serum intact hPTH(1-84) for all treatment regimen
timeFrame: 6 hours
measure: Measurement of serum 1,25-(OH)2D for all treatment regimen (optional)
timeFrame: 6 hours
Locations:
city: Jerusalem
country: Israel
facility: Clinical Research Center Hadassah Ein Kerem Medical Center
Study officials:
affiliation: Clinical Research Center Hadassah Ein Kerem Medical Center
name: Yosef Caraco, MD
role: PRINCIPAL_INVESTIGATOR
References: