A Three Stage, Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of Oral PTH (1-34) in Healthy Subjects

A Double blinded (oral), Open Label, Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of Oral PTH (1-34) in healthy Subjects to establish the safety, tolerability, bioavailability, pharmacokinetic, and pharmacodynamic profile and the of Entera's oral PTH(1 - 34) in adult healthy human volunteers.

Study Overview

• Status: Completed
• Conditions: Drug Safety
• Intervention / Treatment: Drug: Teriparatide; Drug: Teriparatide; Drug: placebo

Detailed Description

This study will have three stages. Stage 1: Safety and initial bioavailability of Entera's oral EP101 in adult male healthy volunteers. (SA-BA) Stage 2: Assessment of bioavailability and safety of Entera's oral EP101 in adult male healthy volunteers. (SA-BA-PK-PD) Stage 3: Safety, PK, and PD of final dose of Entera's oral PTH(1 - 34) in adult healthy male and female volunteers. (SA-BA-PK-PD)

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 91120,
    • HMO Clinical Research Center Hadassah Ein Kerem Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ● Signed Informed consent to the study.

  • Male and female volunteers ,aged 18 - 50 years, BMI 18-30 kg/m2, inclusive,
  • Subjects able to adhere to the visit schedule and protocol requirements
  • Hematology ,Chemistry and Urinalysis values with no clinical significance or do not reflect a medical condition which according to the physicians' judgment might confound the results of the study or pose additional risk to the subject by participation in the study.
  • Hemoglobin level >. 12.5 g/dl
  • Blood pressure levels with no clinical significance.
  • Negative serology to HIV, Hepatitis B, Hepatitis C.
  • No known drug and alcohol abuse
  • Negative urinary drugs of abuse at screening
  • No allergy to soy bean products.
  • No prescription medications taken within one month to enrollment
  • Over-the-counter drugs (including vitamins) taken within 14 days prior to visit 2 are subject to the investigators' discretion for inclusion.
  • No subjects with previous urolithiasis.
  • Non-smoking,
  • In good health as determined by past medical history, physical examination, vital signs, electrocardiogram and laboratory tests at screening

Exclusion Criteria:

• ● Concurrent therapy that, in the Investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study medication.

  • Treatment with any investigational product within the last 30 days, enrollment or intention to enroll in any active study involving the use of investigational devices or drugs.
  • 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.
  • Active infections
  • History of drug or alcohol abuse
  • Known allergies or sensitivities to components of study treatment or study procedures, including Soy.
  • Clinically diagnosed psychiatric disorders that may interfere with patient study participation
  • Medical history known or suspected to increase risks of AEs related to study drug, up to the investigator's discretion
  • Chronic illnesses, up to the investigator's discretion
  • Female subjects must have a negative serum pregnancy test at screening and be willing and able to use a medically acceptable method of birth control (non-hormonal intrauterine device with condom, or diaphragm with condom, or condom with spermicide) from the screening visit through the study termination visit or declare that they are abstaining from sexual intercourse from the screening visit through the study termination visit or are surgically sterile (have undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or post menopausal. Postmenopausal women are defined as women with menstruation cessation for 12 consecutive months prior to signing of the informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Teriparatide group 1; Subcutaneous injection of Teriparatide	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Placebo Comparator: excipients; Oral pill without API	Drug: placebo; Oral placebo
Experimental: API; Oral administration of pill with API	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Experimental: API optimization 1; Oral administration of pill with API, for PK optimization #1	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Experimental: API optimization 2; Oral administration of pill with API, for PK optimization #2	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Experimental: API optimization 3; Oral administration of pill with API, for PK optimization #3	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Experimental: API optimization 4; Oral administration of pill with API, for PK optimization #4	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Experimental: API optimization 5; Oral administration of pill with API, for PK optimization #5	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Experimental: API optimization 6; Oral administration of pill with API, for PK optimization #6	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Experimental: API optimization 7; Oral administration of pill with API, for PK optimization #7	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Active Comparator: Teriparatide group 2; Subcutaneous injection of Teriparatide	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection
Experimental: Excipients; Oral pill without API	Drug: placebo; Oral placebo
Experimental: API Optimized; expanded group size with API in optimized dosage and administration form.	Drug: Teriparatide; single oral tablet; Drug: Teriparatide; subcutaneous standard injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	throughout the study beginning from the time the subject signs the consent form until the end of study, subjects will complete the following evaluations: Vital signs (blood pressure, heart rate, oral temperature); Clinical laboratory evaluations, hematology, chemistry; Physical Exam; ECG	up to 17 weeks

Collaborators and Investigators

• Sponsor: Entera Bio Ltd.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: June 20, 2011
• First Submitted That Met QC Criteria: July 28, 2014
• First Posted (Estimate): July 29, 2014

Study Record Updates

• Last Update Posted (Estimate): October 7, 2015
• Last Update Submitted That Met QC Criteria: October 6, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Teriparatide
• Other Study ID Numbers: 0020-11-HMO-EnteraBio