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

The primary objective of the study is:

• To characterise the pharmacokinetic (PK) profile of teverelix following single dose, subcutaneous (s.c.) and intramuscular (i.m.) administration of teverelix TFA in healthy male subjects

The secondary objectives of the study are:

• To assess the safety and tolerability of teverelix TFA after single s.c. and i.m. injections in healthy male subjects
• To evaluate pharmacodynamics (PD) effects of teverelix following single dose, s.c. and i.m. administration of teverelix TFA in healthy male subjects

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• Receiving an investigational product in a clinical trial within 3 months prior to the screening visit.
• Donation of blood (> 500 mL) or blood products within 2 months (56 days) prior to the screening visit.
• Unwilling to avoid consumption of coffee and caffeine-containing products within 48 hours prior to admission until discharge from the study centre, as well as from 48 hours before ambulatory visits.
• Unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to admission until discharge from the study centre, as well as from 48 hours before ambulatory visits.
• Unwilling to abstain from vigorous exercise from 72 hours prior to admission until discharge from the study centre, as well as from 72 hours before ambulatory visits.
• Unable to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study.
• Subject is unlikely to comply with the protocol requirements, instructions and study related restrictions; e.g., uncooperative attitude, inability to return for follow-up visits and improbability of completing the clinical study.
• Subject has any concurrent condition that, in the opinion of the Principal Investigator, would make the subject unsuitable for participation in the clinical study.
• Subject is an employee or the close relative of an employee of the Sponsor or the clinical research organisation (CRO) involved in the clinical study.
• Vulnerable subjects defined as individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate (e.g., persons in detention, minors and those incapable of giving consent).