A Study to Investigate the Safety, Tolerability, Food Effect, Pharmacokinetics and Pharmacodynamics of FOR-6219

NCT03709420 | Completed Phase 1

• 1 other identifier: 40-533-001
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomised, double-blind, placebo-controlled, Phase I/Ib study which will assess the safety, tolerability, food effect, pharmacokinetics and pharmacodynamics of FOR-6219, a hydroxysteroid (17B) dehydrogenase (HSD17B1) inhibitor. The study will be performed in three parts: (I) Single ascending doses (SAD) in healthy post-menopausal women; (II) multiple ascending doses (MAD) in post-menopausal women; (III) multiple ascending doses in healthy pre-menopausal women.

Conditions

Endometriosis

Keywords

Hydroxysteroid (17B) dehydrogenase; HSD17B1

Outcome Measures

Primary Outcomes (5)

• Safety and tolerability as measured by the incidence of treatment-emergent adverse events (TEAEs).

  All adverse events will be assessed by the investigator and graded for severity according to the criteria from National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) v4.03.

  Throughout the study until the follow-up visit, i.e. 7 days after the last dose in Parts I and II and until day 35 in Part III.

• Proportion of subjects with clinically significant changes in laboratory safety tests.

  Laboratory safety tests include haematology, chemistry, coagulation and urinalysis.

  Throughout the study until the follow-up visit, i.e. 7 days after the last dose in Parts I and II and until day 35 in Part III.

• Proportion of subjects with changes in vital signs (blood pressure, diastolic blood pressure and pulse)

  Vital signs will be measures using automated monitors in supine position after 5 minute rest.

  Throughout the study until the follow-up visit, i.e. 7 days after the last dose in Parts I and II and until day 35 in Part III.

• Proportion of subjects with ECG changes.

  12-lead ECGs and ECG telemetry (only Parts I and II) will be used to measure ECG parameters.

  Throughout the study until the follow-up visit, i.e. 7 days after the last dose in Parts I and II and until day 35 in Part III.

• Presence of any pathology in transvaginal ultrasound (Part III).

  Transvaginal ultrasound will be performed at multiple timepoints.

  Throughout the study until the day of the last dose (day 14).

Secondary Outcomes (9)

• Maximum observed plasma concentration (Cmax).

  Pharmacokinetic measures will be taken predose and multiple timepoints postdose after the single dose (SAD) and up to 72 hours after the last dose (Parts II and III).

• Area under the plasma concentration-time curve (AUC).

  Pharmacokinetic measures will be taken predose and multiple timepoints postdose after the single dose (SAD) and up to 72 hours after the last dose (Parts II and III).

• Time to maximum plasma concentration (Cmax).

  Pharmacokinetic measures will be taken predose and multiple timepoints postdose after the single dose (SAD) and up to 72 hours after the last dose (Parts II and III).

• Terminal half-life (t½).

  Pharmacokinetic measures will be taken predose and multiple timepoints postdose after the single dose (SAD) and up to 72 hours after the last dose (Parts II and III).

• Effect of food on the pharmacokinetic profile of FOR-6219 and metabolite FOR-6287 based on maximum observed plasma concentration (Cmax) (Part II).

  Predose and multiple timepoints post-dose in fed (Day 1) and fasted conditions (Days 3-10).

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching placebo capsule

Drug: Placebo

FOR-6219

EXPERIMENTAL

Part I (SAD): Single oral doses of 2 mg, 10 mg, 25 mg, 50 mg, 100 mg and 175 mg. Part II (MAD): Multiple oral doses of 50 mg QD, 75 mg BID and 150 mg BID. Part III: Multiple oral doses of 10 mg, 25 mg, 75 mg and 150 mg BID

Drug: FOR-6219

Interventions

Placebo DRUG

Placebo capsule to match active drug

Placebo

FOR-6219 DRUG

FOR-6219 capsule

FOR-6219

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Naturally (spontaneously) post-menopausal women or women with bilateral oophorectomy/bilateral salpingo-oophorectomy (Parts I and II) or premenopausal women (Part III).
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Caucasian female volunteers between 45 and 65 years (inclusive) at screening.
• Female volunteers must be either naturally (spontaneously) post-menopausal: Natural (spontaneous) postmenopause is defined as being amenorrheic for at least 12 months without an alternative medical cause with a screening follicle stimulating hormone level \>25.8 IU/L and 17β-oestradiol serum levels less than 183 pmol/L (or the local laboratory levels for post-menopause) OR must have had a bilateral oophorectomy/bilateral salpingo-oophorectomy. Hysterectomised women can be included only if they have had bilateral oophorectomy.
• Volunteers not taking hormone replacement therapy (HRT).
• Has a body weight between 50kg and 100kg inclusive and a body mass index (BMI) between 18.0-32.0 kg/m\^2 inclusive.
• Satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory evaluation (haematology, biochemistry, coagulation and urinalysis) that is reasonably likely to interfere with the volunteer's participation in or ability to complete the study as assessed by the investigator.
• Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guideline E6 (R2) (2016) and applicable regulations, before completing any study-related procedures.
• Ability to swallow multiple capsules at a time or (consecutively) one capsule at a time.
• An understanding, ability, and willingness to fully comply with study procedures and restrictions.

You may not qualify if:

• Post-menopausal women with less than 12 months amenorrhoea or women with amenorrhoea due to other medical causes.
• Current or recurrent disease (e.g., cardiovascular, haematological, neurological, endocrine, immunological, renal, hepatic or gastrointestinal or other conditions) that could affect the action, absorption, or disposition of FOR-6219, or could affect clinical assessments or clinical laboratory evaluations.
• Current or relevant history of physical or psychiatric illness that are not stable or may require a change in treatment, use of prohibited therapies during the study 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.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study may influence the result of the study, or the subject's ability to participate in the study.
• 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.
• Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG or clinically important abnormalities that may interfere with the interpretation of corrected QT (QTc) interval changes.
• Has vital signs consistently outside of the following normal range. Supine blood pressure (after at least 5 minutes of supine rest):
• Systolic blood pressure: 90 - 145 mmHg.
• Diastolic blood pressure: 40 - 95 mmHg.
• Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
• Evidence of pregnancy.
• Any other abnormal findings on vital signs, ECG, physical examination or laboratory evaluation of blood and urine samples that the Investigator judges as likely to interfere with the study or pose an additional risk in participating.
• Positive test results for alcohol or drugs of abuse.
• History or clinical evidence of substance and/or alcohol abuse within the two years before screening.
• 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 three months prior to the planned first day of dosing.

Sponsors & Collaborators

• Forendo Pharma Ltd: lead
• Richmond Pharmacology Limited: collaborator

Study Sites (1)

Richmond Pharmacology Ltd.

London, United Kingdom

Location

MeSH Terms

Conditions

Endometriosis

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Ulrike Lorch, M.D.

  Richmond Pharmacology Limited

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 17, 2018
• Study Start: August 13, 2018
• Primary Completion: November 11, 2020
• Study Completion: November 11, 2020
• Last Updated: November 18, 2020

Record last verified: 2020-11

Locations

GB (1)