Dose Escalation, MTD, Safety and PK Study of a Single Dose SC Injection of TransCon PEG Treprostinil in Healthy Male Volunteers

PAH Clinical Trial

Official title:

A Phase I, Open-label, Dose Escalation Study to Determine the Maximum Tolerated Dose and Evaluate the Safety, Tolerability and Pharmacokinetics of Single Doses of TransCon PEG Treprostinil Administered as a Subcutaneous Injection in Healthy Adult Male Volunteers

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02149095
• Other study ID #: TCP-PH-101
• Status: Withdrawn
• Phase: Phase 1
• First received: May 20, 2014
• Last updated: August 6, 2014
• Start date: July 2014

Study information

• Verified date: August 2014
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

TransCon PEG treprostinil is a novel prodrug form of treprostinil, in which treprostinil is reversibly conjugated via a four-arm branched polyethylene glycol (PEG) molecule. Reversible coupling of treprostinil to PEG should allow for a modified extended pharmacokinetic profile to achieve sustained plasma concentrations of treprostinil.

This will be the first investigation of TransCon PEG treprostinil in humans. This study aims to determine the maximum tolerated dose (MTD) and assess the safety, tolerability and pharmacokinetics of escalating single doses of a subcutaneous injection of TransCon PEG treprostinil.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Subject gives voluntary written informed consent to participate in the study

2. Subject is a healthy male between the ages of 18 and 50 years, inclusive, at Screening

3. Subjects must weigh between 60 and 120 kg, inclusive, with a BMI between 19.0-32.0 kg/m2, inclusive at Screening

4. Subject has a medical history, physical examination, vital signs, ECG and clinical laboratory results within normal limits or considered not clinically significant by the Investigator at Screening

5. Subject agrees to abstain from taking any prescription medication for 14 days prior to check-in and to abstain from taking any non-prescription medications (except multivitamins) or herbal supplements for 7 days prior to check-in Baseline until discharge from the study (unless prescribed by the Investigator to treat an AE)

6. Subject agrees to abstain from consuming alcohol from three days prior to check-in and until discharge from the study

7. Subject agrees to refrain from strenuous exercise from check-in and until discharge from the study

8. Subject is able to communicate effectively with study personnel and be considered reliable, willing and cooperative in terms of compliance with the protocol requirements

Exclusion Criteria:

1. Subject has any clinically relevant abnormality identified during the screening physical examination, 12-lead ECG, or laboratory examinations

2. Subject has a history of anaphylaxis, a previous documented hypersensitivity reaction, or a clinically significant idiosyncratic reaction to any drug

3. Subject has a clinically significant history of neurological, cardiovascular, respiratory, endocrine, hematological, hepatic, renal, gastrointestinal, genitourinary, pulmonary, and/or musculoskeletal disease; glaucoma; a psychiatric disorder, or any other chronic disease, whether controlled by medication or not

4. Subject has a history of postural hypotension, or unexplained syncope

5. Subject has a blood pressure that is less than 85 mmHg systolic or 50 mmHg diastolic at Screening or Baseline

6. Subject has a pulse rate that is greater than 90 bpm after sitting at rest for 5 minutes at Screening or Baseline

7. Subject has a history of hypertension

8. Subject has a blood pressure that is greater than 150 mmHg systolic or 90 mmHg diastolic at Screening or Baseline

9. Subject has a predisposing condition that could interfere with the absorption, distribution, metabolism, or excretion of drugs

10. Subject has tested positive at the screening visit for HIV infection, HBsAg, or the HCV antibody

11. Subject currently uses tobacco products or has a history of tobacco use within six months prior to Baseline

12. Subject has a history of alcohol abuse or a history of or current impairment of organ function reasonably related to alcohol abuse

13. Subject has a history of or current evidence of abuse of licit or illicit drugs or a positive urine screen for drugs of abuse

14. Subject has a history of abnormal bleeding tendencies

15. Subject has donated blood or plasma or has lost a significant volume of blood (greater than 450 mL) within four weeks prior to Baseline

16. Subject has participated in any investigational drug study within 30 days prior to Screening

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• PAH

Intervention

Drug:
• TransCon PEG treprostinil

Locations

Country	Name	City	State
United States	PPD Development	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent AEs		Day 43	Yes
Primary	Maximum tolerated dose		5 days	Yes
Primary	Treatment-emergent changes in clinical laboratory results		43 days	Yes
Primary	Treatment-emergent changes in vital signs		43 days	Yes
Secondary	Area under the concentration versus time curve: (AUC)		42 days	No
Secondary	Maximum observed plasma concentration: Cmax		42 days	No
Secondary	Time to maximum observed plasma concentration: Tmax		42 days	No