Safety, Tolerability and Pharmacokinetics of FTX-6058

• Status: Recruiting
• Trial end date: 2021-12-19
• Target enrollment: 0
• Participant gender: All

Summary

This is a study to evaluate the safety, tolerability and pharmacokinetics of FTX-6058 in healthy adult subjects.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Fulcrum Therapeutics
• Treatments: Midazolam

Criteria

Inclusion Criteria:

• Healthy male / female subjects, 18 to 55 years of age, inclusive at screening.

• Good health, based upon the opinion of the investigator and the results of medical history, physical examination, vital signs, ECG, and laboratory profiles of both blood and urine at screening.

• Body mass index (BMI) between 18 and 32 kg/m2, inclusive at screening, and with a minimum weight of 50 kg.

• Willingness of men and women of reproductive potential to use two effective means of contraception throughout study participation until 90 days after dose administration.

• Females with hematocrit >35% and <45% or hemoglobin >11.7/dL and <15.5/dL and males with hematocrit >38.5% and <50% or hemoglobin >13.2/dL and <17.1/dL.

• Signed and dated written informed consent.

• Willing and able to comply with all study procedures.

Exclusion Criteria:

• History of any illness or any clinical condition that, in the opinion of the investigator/subinvestigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, history or presence of gastrointestinal conditions including Crohn's disease, ulcerative colitis, frequent episodes of diarrhea, or irritable bowel syndrome; history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; clinically significant history of mental disease; concurrent active malignancy; and history of cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 with no recurrence for the last 5 years).

• History of febrile illness within 1 week prior to the baseline visit.

• Acute or chronic history of liver disease or current alanine aminotransferase ≥2 × ULN or total bilirubin >1.5 × ULN at screening (note: subjects with Gilbert's syndrome are permitted to enroll in the trial).

• Known renal impairment (defined as glomerular filtration rate of <60 mL/min/1.73 m2).

• Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency viruses 1 and 2 (HIV1/HIV2 Abs) at screening.

• Any condition possibly affecting drug absorption (e.g., gastrectomy, cholecystectomy, or other gastrointestinal tract surgery, except appendectomy).

• Standard 12 lead ECG demonstrating QTcF >450 msec for male subjects and QTcF >470 msec for female subjects at screening. If QTcF exceeds 450 msec for males or 470 msec for females, the ECG will be repeated 2 more times, and the average of the 3 QTcF values will be used to determine the subject's eligibility.

• History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s) or history or evidence of abnormal ECGs that, in the opinion of the investigator or medical monitor, would preclude the subject's participation in the study.

• Blood or blood product (e.g., plasma/serum) donation (of approximately 1 pint [500 mL] or more) or any significant loss of blood within 8 weeks prior to screening or intention to donate blood or blood products during the study as determined by the investigator.

• History of abuse of addictive substances such as drug abuse, or regular user of sedatives, hypnotics, tranquillizers, or any other addictive agent within 6 months prior to screening.

• History of regular alcohol consumption within 6 months prior to screening defined as:

• An average weekly intake of greater than 21 units. One unit is equivalent to a 285 mL glass of full-strength beer or 425 mL of light beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine.

• History of demonstrating an excess in xanthine or caffeine consumption (more than 8 cups of coffee or equivalent per day).

• Use of another investigational product within 30 days or 5 half-lives (whichever is longer), or according to local regulations, or currently participating in a prospective study with an investigational product or medical device.

• Use of any medication (prescription or over-the-counter [OTC]) within 14 days of study drug administration, or use of herbal supplements, dietary supplements or multivitamins within 7 days of study drug administration or less than 5 half-lives (whichever is longer), with the exception of paracetamol (up to 3 g/day). Other exceptions will only be made if the rationale is clearly documented by the investigator. Note: Any vaccination, including COVID-19 vaccine, cannot be administered within 14 days prior to initial dose of study drug until the end of study participation.

• History of sensitivity to the study drug or placebo, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.

• Female subject who is pregnant, trying to become pregnant, or is breastfeeding or male subject whose partner is pregnant, trying to become pregnant, or is breastfeeding.

• Subject is mentally or legally incapacitated.

• Abnormal laboratory results indicative of any significant medical disease that, in the opinion of the investigator, would preclude the subject's participation in the study at screening or prior to first dose.

• Subject, or close relative of the subject, is the investigator or a subinvestigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site.

• Positive test for drugs of abuse at screening or baseline.

• Positive test for COVID-19 prior to admission to the study site, as required per local regulations.

• Subject smokes cigarettes (or equivalent) and/or has used nicotine-based products within 3 months prior to screening. Note: Cotinine test is not required per protocol but may be performed at the discretion of the Investigator to confirm non-smoker status.

• Consumption of any alcohol within the 48-hour period prior to study drug administration.

• Plans for hospitalization, surgery, or other major procedures during the study duration or between screening and baseline.

• Part D only: Any contraindication to the use of midazolam.