An Open-label Study in Healthy Participants to Evaluate AZD0780 as an Object or Precipitant of CYP3A4-mediated Drug-drug Interactions

NCT06671405 | Completed Phase 1 FDA Drug

• 1 other identifier: D7960C00011
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, fixed sequence study in healthy participants to assess the pharmacokinetics of AZD0780 when administered alone and in combination with itraconazole and carbamazepine, and to assess the pharmacokinetics of midazolam and ethinyl estradiol/levonorgestrel (EE and LNG) when administered alone and in combination with AZD0780.

Conditions

Dyslipidaemia

Outcome Measures

Primary Outcomes (6)

• AUCinf (Area under concentration-time curve from time 0 to infinity)

  To describe the PK of AZD0780 when administered alone and in combination with itraconazole and carbamazepine.

  Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)

• AUClast (Area under concentration curve from time 0 to the last quantifiable concentration)

  To describe the PK of AZD0780 when administered alone and in combination with itraconazole and carbamazepine.

  Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)

• Cmax (Maximum observed drug concentration)

  To describe the PK of AZD0780 when administered alone and in combination with itraconazole and carbamazepine.

  Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)

• AUCinf

  To assess the effect of AZD0780 on the PK of midazolam (Part 3) and EE and LNG (Part 4).

  Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)

• AUClast

  To assess the effect of AZD0780 on the PK of midazolam (Part 3) and EE and LNG (Part 4).

  Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)

• Cmax

  To assess the effect of AZD0780 on the PK of midazolam (Part 3) and EE and LNG (Part 4).

  Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)

Secondary Outcomes (11)

• CL/F (Apparent total body clearance)

  Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)

• t½λz (Terminal elimination half-life)

  Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)

• tmax (Time to reach maximum observed concentration)

  Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)

• Vz/F (Apparent volume of distribution based on the terminal phase)

  Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)

• Number of participants with Adverse Events and Serious Adverse Events (AEs and SAEs)

  From Baseline until Follow-up Visit (7 to 14 days post-discharge)

Study Arms (4)

Itraconazole Cohort

EXPERIMENTAL

* All participants will receive 2 single doses of dose 1 of AZD0780 and 14 doses of itraconazole, under fed conditions. * This part will consist of Period 1 (AZD0780 administration only), Period 2 (itraconazole administration only), and Period 3 (AZD0780 + itraconazole administration).

Drug: AZD0780; Drug: Itraconazole

Carbamazepine Cohort

EXPERIMENTAL

* All participants will receive 2 single doses of dose 1 of AZD0780 and 6 doses of 100 mg, 6 doses of 200 mg, and 40 doses of 300 mg carbamazepine, under fed conditions. * This part will consist of Period 1 (AZD0780 administration only), Period 2 (carbamazepine administration only), and Period 3 (AZD0780 + carbamazepine administration)

Drug: AZD0780; Drug: Carbamazepine

Midazolam Cohort

EXPERIMENTAL

* All participants will receive 10 single doses of AZD0780 dose 2 and 2 doses of midazolam. On midazolam dosing days, participants will receive midazolam under fasted conditions. * This part will consist of Period 1 (midazolam administration only), Period 2 (AZD0780 administration only), and Period 3 (AZD0780 + midazolam administration).

Drug: AZD0780; Drug: Midazolam

EE and LNG Cohort

EXPERIMENTAL

* All participants will receive 15 single doses of AZD0780 dose 2 and 2 doses of EE and LNG. On EE and LNG dosing days, participants will receive EE and LNG under fasted conditions. * This part will consist of Period 1 (EE and LNG administration only), Period 2 (AZD0780 administration only), and Period 3 (AZD0780 + EE and LNG administration).

Drug: AZD0780; Drug: Ethinyl estradiol/levonorgestrel

Interventions

AZD0780 DRUG

Dose 1 and Dose 2

Carbamazepine Cohort; EE and LNG Cohort; Itraconazole Cohort; Midazolam Cohort

Itraconazole DRUG

* Period 2 (itraconazole administration only). * Period 3 (AZD0780 + itraconazole administration).

Itraconazole Cohort

Carbamazepine DRUG

* Period 2 (carbamazepine administration only). * Period 3 (AZD0780 + carbamazepine administration only).

Carbamazepine Cohort

Midazolam DRUG

* Period 1 (midazolam administration only). * Period 3 (AZD0780 + midazolam administration).

Midazolam Cohort

Ethinyl estradiol/levonorgestrel DRUG

* Period 1 (EE and LNG administration only). * Period 3 (AZD0780 + EE and LNG administration).

EE and LNG Cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study-specific procedures.
• Healthy male and female participants of non-childbearing potential aged 18 to 75 years with suitable veins for cannulation or repeated venipuncture. Part 4 only: Healthy female participants of non-childbearing potential aged 18 to 75 years with suitable veins for cannulation or repeated venipuncture.
• All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
• Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria:
• Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation or tubal occlusion.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods detailed in Appendix C 2.1 from the time of first administration of AZD0780 administration until 3 months after the study Follow-up Visit.
• Have a BMI between 18 and 35 kg/m2 inclusive and weight at least 50 kg at the Screening Visit and on admission to the Clinical Unit.

You may not qualify if:

• History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any prior gastrointestinal surgery which may affect absorption, eg, gastric bypass or resection.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
• Any laboratory values with the following deviations at the Screening Visit or on admission to the Clinical Unit. Abnormal values may be repeated once at the discretion of the Investigator.
• Any positive result at Screening for serum HBsAg, HBcAb, HCV, or HIV.
• Any clinically significant abnormal findings in abnormal vital signs, after at least 10 minutes supine rest, at Screening and on admission to the Clinical Unit, as judged by the Investigator. Abnormal values may be repeated once at the discretion of the Investigator..
• Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QTc interval changes.
• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months prior to screening.
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the Investigator.
• Positive screen for drugs of abuse, alcohol, or cotinine at Screening or on admission to the Clinical Unit.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD0780, itraconazole (Part 1 only), carbamazepine (Part 2 only), midazolam (Part 3 only), or EE/LNG (Part 4 only).
• Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) defined as the regular consumption of more than 500 mg of caffeine per day (eg, \> 5 cups of coffee \[one cup \~100 mg caffeine\]; one cup of tea \~30 mg caffeine) or would likely be unable to refrain from the use of caffeine-containing beverages during confinement at the Clinical Unit.
• Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of study intervention.
• Use of any prescribed or nonprescribed medication including hormone replacement therapy, antacids or acid reducing agents (including proton pump inhibitors),analgesics (other than paracetamol/acetaminophen), herbal remedies, mega dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of study intervention or longer if the medication has a long half-life.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Dyslipidemias

Interventions

Itraconazole; Carbamazepine; Midazolam; Ethinyl Estradiol-Norgestrel Combination

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Ethinyl Estradiol; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Norgestrel; Norpregnenes; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: DDI study, open label, fixed sequence

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: November 4, 2024
• Study Start: September 25, 2024
• Primary Completion: February 17, 2025
• Study Completion: February 17, 2025
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

US (1)