Drug-Drug Interaction Study to Evaluate the Pharmacokinetics and Safety of CTX 4430 and Midazolam

Celtaxsys

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Midazolam

Drug: CTX-4430

Study type

Interventional

Funder types

Other

Identifiers

NCT02233244

CTX-4430-DI-001

Details and patient eligibility

About

This drug-drug interaction study will assess the potential of CTX-4430 to induce CYP3A activity in healthy subjects.

The study hypothesis is that midazolam (a sensitive, widely used CYP3A4 substrate) blood levels will not change after treatment with CTX-4430.

Enrollment

20 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy adult male or female, 18-55 years of age, inclusive at screening
Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose
Body Mass Index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening
Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI
For a female of childbearing potential: either be sexually inactive (true abstinence in line with the preferred and usual lifestyle of the subject) for 14 days prior to the first dose and throughout the study or be using one of the following acceptable birth control methods:
1. non-hormone releasing intrauterine device in place for at least 3 months prior to the first dose with a physical (e.g. condom or diaphragm or other) and a chemical barrier (e.g. spermicide) from the time of screening through 14 days following the last dose
2. double physical barrier (e.g. condom and diaphragm or other) and a chemical barrier (e.g. spermicide) from the time of screening through 14 days following the last dose
3. surgical sterilization of the partner (vasectomy for 180 days minimum) with a physical (e.g. condom or diaphragm or other) and a chemical barrier (e.g. spermicide) from the time of screening through 14 days following the last dose.
4. or have an exclusive non-heterosexual lifestyle
In addition, female subjects of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method for at least 14 days following the last dose
Female of non childbearing potential: must have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
1. hysteroscopy sterilization (with a copy of the confirmation test) and be using a physical (e.g. condom or diaphragm or other) and a chemical barrier (e.g. spermicide) a barrier method (e.g., condom or diaphragm) with spermicide throughout the study
2. bilateral tubal ligation or bilateral salpingectomy and be using a physical (e.g. condom or diaphragm or other) and a chemical barrier (e.g. spermicide) a barrier method (e.g., condom or diaphragm) with spermicide throughout the study
3. hysterectomy
4. bilateral oophorectomy or be postmenopausal with amenorrhea for at least 1 year prior to the first dose and FSH serum levels consistent with postmenopausal status
A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to study start. A male who has been vasectomized less than 4 months prior to study start must follow the same restrictions as a non vasectomized male)
If male, must agree not to donate sperm from the first dose until 90 days after dosing
A subject who claims to be sexually inactive needs to remain inactive for the whole study duration
Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol

Exclusion criteria

Subject is mentally or legally incapacitated or has significant emotional problems at the time of screening visit or expected during the conduct of the study
History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI
History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study
History or presence of chronic alcohol or drug abuse the past 2 years prior to screening
History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds (e.g., any other benzodiazepine for midazolam since cross sensitivity with other benzodiazepines is possible) or any component of the midazolam solution formulation
Subject is currently taking or has a history of pronounced sedation upon taking benzodiazepines or other sedative/soporific drugs
Female subjects who are pregnant or lactating
Positive urine drug results at screening or check-in or positive alcohol results at check in
Drink alcohol in excess of 21 glasses/units per week for males or 14 glasses/units per week for females, with one unit = 150 mL of wine or 360 mL of beer or 45 mL of 45% alcohol
Positive urine cotinine at screening
Positive results at screening for HIV, HBsAg or HCV
Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening
Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening
QTcF interval is >430 msec (males) or >450 msec (females) or deemed clinically abnormal by the PI
Unable to refrain from or anticipates the use of:
- Any drug, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dose of study drug and throughout the study. Hormonal contraceptives and hormone replacement therapy will not be allowed. Paracetamol (up to 2 g per 24 hour period) may be permitted during the study.
- Any drugs, foods, or herbal preparations known to be significant inducers of CYP enzymes and/or Pgp, including St. John's Wort, for 28 days prior to the first dose of study drug and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of PK/PD interaction with study drug.
Have been on a diet incompatible with the on study diet, in the opinion of the PI, within the 28 days prior to the first dose of study drug(s), and throughout the study
Donation of blood or plasma within 90 days prior to the first dose of study drug
Donation of bone marrow within the last 6 months prior to the first dose of study drug
Participation in another clinical trial within 90 days prior to the first dose of study drug. The 90 day window will be derived from the date of the last study scheduled blood collection