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

NCT02233244 | Completed Phase 1

• 1 other identifier: CTX-4430-DI-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Drug Interaction

Outcome Measures

Primary Outcomes (1)

• To evaluate the change in maximum plasma concentration (Cmax) and area under the curve (AUC) for both midazolam and 1-OH-midazolam after 7 days of treatment with CTX-4430

  10 days

Secondary Outcomes (2)

• To evaluate the safety and tolerability of the administration of single oral doses of midazolam, both in the absence and presence of multiple dose CTX-4430.

  10 days

• To evaluate the safety and tolerability of multiple oral doses of CTX-4430.

  10 days

Study Arms (1)

CTX-4430 and midazolam

OTHER

Midazolam 2 mg solution once, CTX-4430 100 mg tablet once per day for 7 days, Midazolam 2 mg solution once

Drug: CTX-4430; Drug: Midazolam

Interventions

CTX-4430 DRUG

CTX-4430 and midazolam

Midazolam DRUG

CTX-4430 and midazolam

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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
• 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
• 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.
• 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:
• 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
• 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
• hysterectomy
• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Celtaxsys, Inc.: lead

Study Sites (1)

Celerion

Belfast, BT9 6AD, United Kingdom

Location

MeSH Terms

Interventions

acebilustat; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Johnston Stewart, MB, BSc

  Celerion Belfast, Northern Ireland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: September 8, 2014
• Study Start: September 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 10, 2014

Record last verified: 2014-10

Locations

GB (1)