Clinical trial: A Study to Investigate the Effects of Cortexolone 17α-propionate (and Its Metabolites) on Healthy Volunteers' Heart (NCT03665194)

Eligibility criteria:
Inclusion Criteria:

          1. Male or female subjects ≥18 and ≤40 years at the date of signing informed consent
             which is defined as the beginning of the Screening Period.

          2. Subjects must have a body mass index (BMI) between 18.0-25.0 kg/m² inclusive.

          3. Subjects must be bald, have a shaved head, or be willing to have their head shaved.

          4. Female subjects who are either: (a) Non-childbearing potential, e.g. post-menopausal
             (as defined as amenorrhoea for at least 12 months with no alternative medical cause)
             or permanently sterile (permanent sterilisation methods include hysterectomy,
             bilateral salpingectomy and bilateral oophorectomy) OR (b) Childbearing potential AND
             (if heterosexually active) agree to use at least one form of highly effective
             contraception as defined below, starting at least one menstrual cycle before first
             study drug administration and continuing until at least 3 months after the end of the
             systemic exposure of the study drug.

             Highly effective contraceptive methods for females are as follows:

               -  Combined (oestrogen- and progestogen-containing) hormonal contraception
                  associated with inhibition of ovulation as follows:

                    -  Oral

                    -  Intravaginal

                    -  Transdermal

               -  Progestogen-only hormonal contraception associated with inhibition of ovulation
                  as follows: o Oral

                    -  Injectable

                    -  Implantable

               -  Intrauterine device (IUD)

               -  Intrauterine hormone-releasing system (IUS)

               -  Bilateral tubal occlusion

               -  Male partner vasectomised (with documented evidence of azoospermia if possible)

          5. Male subjects, if heterosexually active and with a female partner of childbearing
             potential or a pregnant or breastfeeding partner, must agree to use barrier
             contraception (male condom) for the treatment period and for at least three months
             after the end of the systemic exposure of the study drug. Female partners of male
             subjects who are of childbearing potential must use one or more forms of highly
             effective contraception as defined above, starting at least one menstrual cycle before
             (their male subject's) first study drug administration and continuing until at least
             three months after the end of their male partner's systemic exposure to the study
             drug.

             For male subjects who have had a vasectomy (with documented evidence of azoospermia if
             possible) and agree to use a barrier method (male condom) for the stated time period,
             no additional contraceptive method is required by their female partner.

          6. Subjects must agree not to donate sperm or ova from the time of the first
             administration of study medication until 3 months after the end of the systemic
             exposure of the study drug.

          7. Satisfactory medical assessment with no clinically significant or relevant
             abnormalities as determined by medical history, physical examination, vital signs,
             12-lead ECG, and clinical laboratory evaluation (haematology, biochemistry,
             coagulation and urinalysis) that is reasonably likely to interfere with the subject's
             participation in or ability to complete the study as assessed by the investigator.

          8. Ability to provide written, personally signed, and dated informed consent to
             participate in the study, in accordance with the ICH Good Clinical Practice (GCP)
             Guideline E6 (1996) and applicable regulations, before completing any study-related
             procedures.

          9. An understanding, ability, and willingness to fully comply with study procedures and
             restrictions.

        Exclusion Criteria:

          1. Current or recurrent disease (e.g., cardiovascular, haematological, neurological,
             endocrine, renal, liver, gastrointestinal, hepatic or other conditions) that could
             affect the action, absorption, or disposition of Cortexolone 17α-propionate, or could
             affect clinical assessments or clinical laboratory evaluations.

          2. Current or relevant history of any physical or psychiatric illness that may require
             treatment or make the subject unlikely to fully comply with the requirements of the
             study or complete the study, or any condition that presents undue risk from the
             investigational product or study procedures.

          3. Any other significant disease or disorder which, in the opinion of the investigator,
             may put the subject at unacceptable risk because of participation in the study, may
             influence the result of the study, or may affect the subject's ability to participate
             in the study.

          4. History of any pathology affecting the skin such as eczema, psoriasis or any skin
             hypersensitivity.

          5. Have tattoos on the scalp or thigh which would affect the area for topical application
             of the trial drug.

          6. The history or presence of any of the following cardiac conditions: known structural
             cardiac abnormalities; family history of long QT syndrome; cardiac syncope or
             recurrent, idiopathic syncope; exercise related clinically significant cardiac events.

          7. Any clinically significant abnormalities in rhythm, conduction or morphology of
             resting ECG or clinically important abnormalities that may interfere with the
             interpretation of QTc interval changes. This includes subjects with any of the
             following (at screening, Day -1 or pre-dose of Day 1):

               -  Sinus node dysfunction.

               -  Clinically significant PR (PQ) interval prolongation.

               -  Intermittent second or third degree AV block.

               -  Complete bundle branch block.

               -  Sustained cardiac arrhythmia's including (but not limited to) atrial fibrillation
                  or supraventricular tachycardia; any symptomatic arrhythmia with the exception of
                  isolated extra systoles.

               -  More than 200 ventricular ectopic beats in 24 hours.

               -  Ventricular tachycardia (ventricular tachycardia defined as ≥ 3 successive
                  ventricular ectopic beats at a rate of > 120 bpm).

               -  Abnormal T wave morphology.

               -  QT interval corrected using the Fridericia's formula (QTcF) > 450 ms.

               -  Any other ECG abnormalities in the standard 12-lead ECG and 24-hour 12 lead
                  Holter ECG or an equivalent assessment which in the opinion of the investigator
                  will interfere with the ECG analysis.

             Subjects with borderline abnormalities may be included if the deviations do not pose a
             safety risk, and if agreed between the appointed Cardiologist and the investigator.

          8. Has vital signs outside of the following normal range at screening, Day -1 or Day 1
             predose:

               1. Blood pressure (BP):

                  Supine BP (after at least 5 minutes of supine rest):

                    -  Systolic blood pressure: 90 - 140 mmHg.

                    -  Diastolic blood pressure: 40 - 90 mmHg.

               2. Supine pulse rate after at least 5 minutes of rest: 45 - 100 bpm .

          9. Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
             or human immunodeficiency virus antibody (HIV Ab) at screening;

         10. Subjects who are pregnant, breast feeding or lactating.

         11. Any clinically relevant abnormal laboratory results (including hepatic and renal
             panels, complete blood count, chemistry panel, coagulation and urinalysis), and vital
             signs, or physical findings at screening, pre-dose of Day 1 (as judged by the
             investigator). In case of uncertain or questionable results, tests performed during
             screening may be repeated before randomization to confirm eligibility or judged to be
             clinically irrelevant for healthy subjects.

         12. Positive test results for alcohol or drugs of abuse at screening or Day -1.

         13. Presence or history of drug or alcohol abuse in the last 5 years, or the inability to
             refrain from alcohol use from 48 hours before screening, dosing and each scheduled
             visit until the end of the study. Alcohol abuse is defined as regular weekly intake of
             more than 14 units, using the following NHS alcohol tracker
             http://www.nhs.uk/Tools/Pages/drinks-tracker.aspx.

         14. Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing
             products in any form (e.g., gum, patch, electronic cigarettes) within 3 months prior
             to the planned first day of dosing.

         15. Use of prescription medications within 14 days or 10 half-lives (whichever is longer)
             prior to Day 1 of the dosing period, or any over-the-counter (OTC) medication
             (including multivitamin, herbal, or homeopathic preparations, excluding hormonal
             contraception, hormone-replacement therapy, and/or an occasional dose of
             acetaminophen) within 7 days prior to Day 1 of the dosing period.

         16. Consumption of herbal remedies or dietary supplements containing St. John's Wort in
             the three weeks before the planned Day 1 of the dosing period.

         17. Consumption of drugs or other substances known to be potent inhibitors or inducers of
             CYP P450s in the three weeks before the planned Day 1 of the dosing period. This
             includes food or drink products containing cranberry, pomegranate, star fruit,
             grapefruit, pomelos, exotic citrus fruits or Seville oranges (including marmalade and
             juices made from these fruits).

         18. Consumption of caffeine, caffeine-containing or xanthine-containing products, energy
             drinks containing taurine or glucuronolactone within 48 hours prior to the planned
             first study drug administration.

         19. Has received an investigational product or been treated with an investigational device
             within 90 days prior to first drug administration and will not start any other
             investigational product or device study within 90 days after last study drug
             administration.

         20. Known or suspected intolerance or hypersensitivity to the investigational product, any
             closely related compound or any of the stated ingredients.

         21. History of significant allergic reaction (anaphylaxis, angioedema) to any product
             (food, pharmaceutical, etc).

         22. Has donated or lost 400 mL blood or more within the last 16 weeks preceding the first
             day of dosing.

         23. Has a mental incapacity or language barriers precluding adequate understanding,
             co-operation, and compliance with the study requirements.

             Cassiopea S.p.A. CONFIDENTIAL 30 April 2018 Protocol Ref: CB-03-01/33 Final Version
             5.0 Page 30 of 43 RPL Study No. C16021 C16021_Protocol_v5.0_30Apr2018

         24. An inability to follow a standardized diet and meal schedule or inability to fast, as
             required during the study.

         25. Prior screen failure (where the cause of the screen failure is not deemed to be
             temporary), randomization, participation, or enrolment in this study. Subjects who
             initially failed due to temporary non-medically significant issues are eligible for
             re-screening once the cause has resolved.

         26. Objection by the General Practitioner (GP) to the subject entering the study.

         27. Subjects with any medical history, conditions, or risks that, in the opinion of the
             investigator, may interfere with the subject's full participation in the study or
             compliance with the protocol, or may pose any additional risk for the subject or
             confound the assessment of the subject or outcome of the study.

             -
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 40 Years

Patient description (medical language): A 30-year-old man who is a computer scientist came to the clinic with the lab result stating azoospermia.  The patient is sexually active with his wife and does not use any contraception methods.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia, shortness of breath, and  persistent cough that produces large amounts of thick sputum. The patient had multiple lung infections during childhood. He does not smoke, use illicit drugs or alcohol.  The patient has no history of other medical conditions including allergies or any kind of surgery.  On physical examination, the digits show clubbing.  An ultrasound shows bilateral absence of the vas deferens, and FEV1 was 75% on the respiratory function test.

Patient description (patient's own words): I'm a 30-year-old computer scientist. I did some lab tests that came back quite alarming, stating that I have azoospermia?! I'm sexually active with my wife and we don't use contraception. We've been trying to have a child for the past year. I have a medical history of pneumonia and shortness of breath and regular wet cough. I had several lung infections when I was a kid. That's why I'm very careful and don't smoke, do drugs, or drink. I don't have other medical conditions including allergies or any kind of surgery. The doctor did the clubbing test on my fingers, which was positive. I also did an ultrasound and it showed that I'm missing the tubes that carry sperm around. I also had a 75% for my respiratory function test.

Does the patient match the trial criteria? 0