A Study of Parenterally-administered Teverelix TFA in Healthy Male Volunteers

NCT03781947 | Completed Phase 1

• 1 other identifier: ANT-1111-P01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I, open-label, single centre study investigating the pharmacokinetics, safety and pharmacodynamics of a single dose of teverelix TFA, a gonadotrophin releasing hormone antagonist, via subcutaneous or intramuscular route of administration in healthy male volunteers

Conditions

Healthy

Outcome Measures

Primary Outcomes (12)

• AUC0-t

  Area under the concentration time-curve from time zero up to the last measurable concentration at time point t Area under the concentration time-curve from time zero up to the last measurable concentration at time point t Area under the concentration time-curve from time zero up to the last measurable concentration at time point t

  12 weeks

• AUC0-t1

  Area under the concentration time-curve from time zero up to concentration at time point t1 after which the concentrations start to rise again towards a second peak, t1 will be determined after review of the concentration-time profiles (immediate release component of total observed AUC)

  12 weeks

• AUCt1-t

  Area under the concentration time-curve from time point t1 up to time point t (slow release component of total observed AUC)

  12 weeks

• AUC0-∞

  Area under the concentration time-curve from time zero up to infinity (∞)

  12 weeks

• Cmax

  Maximum observed concentration after administration

  12 weeks

• Cmax,0-t1

  Maximum observed concentration after administration from zero up to time point t1

  12 weeks

• Cmax,t1-t

  Maximum observed concentration after administration from time point t1 up to time point t

  12 weeks

• Tmax

  Time to reach Cmax after dosing

  12 weeks

• Tmax,0-t1

  Time to reach Cmax,0-t1 after dosing

  12 weeks

• Tmax,t1-t

  Time to reach Cmax,t1-t after dosing

  12 weeks

• λz

  Apparent terminal rate constant

  12 weeks

• t½

  Apparent terminal plasma half-life

  12 weeks

Secondary Outcomes (4)

• Systemic tolerability - Incidence of Treatment-Emergent Adverse Events

  12 weeks

• Local tolerability - Standardised Injection Site Reaction Scoring System (4-point) plus photography

  12 weeks

• Cardiac assessments

  12 weeks

• 24 hour Holter monitoring

  Day -1 to Day 1

Other Outcomes (3)

• Testosterone (total) levels

  12 weeks

• Luteinising Hormone (LH) levels

  12 weeks

• Follicle Stimulating Hormone (FSH) levels

  12 weeks

Study Arms (4)

90 mg s.c.

EXPERIMENTAL

A single s.c. injection of 90 mg teverelix TFA administered on Day 1

Drug: teverelix TFA

60 mg s.c.

EXPERIMENTAL

A single s.c. injection of 60 mg teverelix TFA administered on Day 1

Drug: teverelix TFA

90 mg i.m.

EXPERIMENTAL

A single i.m. injection of 90 mg teverelix TFA administered on Day 1

Drug: teverelix TFA

120 mg s.c.

EXPERIMENTAL

A single s.c. injection of 120 mg teverelix TFA administered on Day 1

Drug: teverelix TFA

Interventions

teverelix TFA DRUG

A single s.c. or i.m. injection of teverelix TFA administered on Day 1

120 mg s.c.; 60 mg s.c.; 90 mg i.m.; 90 mg s.c.

Eligibility Criteria

• Age: 40 Years - 70 Years
• Gender Eligibility Details: Healthy male volunteers
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide voluntarily agreement to participate in this study and sign an Independent Ethics Committee (IEC)-approved informed consent prior to performing any of the screening procedures.
• Males of any ethnic origin, between 40 to 70 years of age (inclusive) at the screening visit.
• Healthy, determined by pre-study medical evaluation (medical history, vital signs, physical examination, standard 12-lead ECG and clinical laboratory evaluations).
• If a vital sign or ECG assessment is outside of the reference range at the screening visit or admission, the assessment may be repeated once to rule out any error.
• Body mass index (BMI) between 20.0 and 34.9 kg/m2 (inclusive) at the screening visit and on admission.

You may not qualify if:

• Clinically relevant history of cardiovascular, respiratory, hepatic, renal, pancreatic, gastrointestinal, metabolic, endocrine, neurological, dermatological, immunological, psychiatric or other diseases/disorders as determined by the Principal Investigator or designee, or evidence of such diseases/disorders during the screening period.
• Any disorder or clinically relevant surgical history that would interfere with the absorption, distribution, metabolism or excretion of the study drug.
• History of proneness to orthostatic dysregulation, fainting or blackouts.
• History or physical evidence of chronic or clinically relevant acute infection.
• Screening total testosterone \<3.0 ng/mL (\<10.4 nmol/L).
• History of anaphylactoid reactions or hypersensitivity to teverelix or GnRH antagonists or any of the excipients of the products tested.
• History of clinically relevant allergies or idiosyncrasies to medication or food.
• History of regular alcohol consumption exceeding 21 units per week within 2 years of study entry.
• History of illicit drug abuse within 2 years of study entry.
• Any ECG abnormality of clinical relevance; ECG QT interval corrected for heart rate using Fridericia's correction (QTcF) \> 450 ms at the screening visit.
• Any clinically relevant findings in the laboratory tests, as judged by the Principal Investigator, at the screening visit and on admission; alanine aminotransferase (ALT) \> 1.5 x the upper limit of normal (ULN) and/or aspartate aminotransferase (AST) \> 1.5 x ULN and/or total bilirubin \> 1.0 x ULN, as confirmed by subsequent repeat assessment, at the screening visit and on admission. If a laboratory assessment is outside of the reference range at the screening visit or admission, the assessment may be repeated once to rule out laboratory error.
• An estimated glomerular filtration rate (eGFR) \< 90 mL/min, based on creatinine clearance calculation by the Cockcroft Gault formula and normalised to an average surface area of 1.73m2, at the screening visit.
• Positive results in any of the tests for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), hepatitis C antibody (anti-HCV) or human immunodeficiency virus (HIV) antibodies, at the screening visit.
• Positive urine test for ethanol and/or drugs of abuse at the screening visit or admission.
• Use of prescription, non-prescription and over-the-counter (OTC) medications (including vitamins or herbal remedies) within 2 weeks prior to dosing is prohibited.

Sponsors & Collaborators

• Antev Ltd.: lead

Study Sites (1)

PAREXEL International Early Phase Clinical Unit (EPCU)

London, Middlesex, HA1 3UJ, United Kingdom

Location

Study Officials

• Pablo Forte Soto, MD

  Parexel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This Phase I clinical study is an open-label, parallel-design, single-centre study to investigate the PK, safety and PD following subcutaneous and intramuscular administration of single doses of teverelix TFA in healthy male subjects.

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: December 20, 2018
• Study Start: November 19, 2018
• Primary Completion: March 16, 2020
• Study Completion: March 16, 2020
• Last Updated: March 17, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)