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Healthy ParticipantsPhase 1NCT05395117

A Study to Assess the Effect of AZD5462 on the Pharmacokinetics of Midazolam, Rosuvastatin and Digoxin

A Phase 1 study testing AZD5462, Midazolam and Rosuvastatin in people with Healthy Participants, run by AstraZeneca at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will assess the effect of multiple doses of AZD5462 on the PK of oral midazolam (CYP3A4 probe), rosuvastatin (OATP1B1/3, BCRP probe), and digoxin (P-gp probe) in healthy participants. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Participants
What is being tested?
AZD5462, Midazolam and Rosuvastatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
30 Jun 2022to 12 Sep 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Provision of signed and dated, written informed consent prior to any study specific procedures.
  • Healthy male and female participants aged 18 to 55 years with suitable veins for cannulation or repeated venepuncture.
  • Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non childbearing potential confirmed at screening.
  • Have a Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 50 kg and no more than 105 kg inclusive at screening.
  • Male subject must adhere to the contraception methods details.

Who cannot join

  • History of any clinically significant disease or disorder which 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 including but not limited to:
  • Systemic sclerosis (ie, scleroderma). (ii) Moderate to severe valvular disease. (iii) Hypertrophic obstructive cardiomyopathy. (iv) Restrictive cardiomyopathy. (v) Gilbert's syndrome. (vi) History of vascular or left ventricular aneurysms or prior dissections. (vii) Any history of joint hypermobility, Marfan's Syndrome, or any connective tissue disorder.
  • 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 clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMPs.
  • Any laboratory values with deviations at screening or admission to the study centre.
  • Any clinically significant abnormalities in clinical biochemistry, haematology, or urinalysis results.
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  • Any clinically significant abnormal findings in vital signs after 5 minutes supine rest.
  • Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG.
  • Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
  • Known or suspected history of drug abuse.
  • Has received another new chemical entity within 3 months of the first administration of IMP in this study.
  • Plasma donation within 1 month of screening or any blood donation/loss > 500 mL during the 3 months prior to screening.
  • History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5462.
  • Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening.
  • Positive screen for drugs of abuse or cotinine at screening or on each admission to the study centre or positive screen for alcohol on admission to the study centre prior to the first administration of the IMP.
  • Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
  • Use of any prescribed or non prescribed medication including antacids, analgesics, herbal remedies, megadose vitamins and minerals during the 2 weeks or 5 half-lives of the medication, whichever is longer, prior to the first administration of IMP.
  • Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
  • Excessive intake of caffeine-containing drinks or food.
  • Involvement of any AstraZeneca, Parexel, or study centre employee or their close relatives.
  • Participants who have previously received AZD5462.
  • Participants who are vegans or have medical dietary restrictions.
  • Vulnerable participants.
  • Participants who cannot communicate reliably with the Principal Investigator (PI).
  • Clinical signs and symptoms consistent with COVID-19 by appropriate laboratory test within the last 4 weeks prior to screening or on admission.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Research Site

    Brooklyn, Maryland, 21225

Other trials in United States

About this study

Official title: A Fixed Sequence, Open-label Study to Assess the Effect of Multiple Doses of AZD5462 on the Pharmacokinetics of Oral Midazolam (CYP3A4 Probe), Rosuvastatin (OATP1B1/3, BCRP Probe), and Digoxin (P-gp Probe) in Healthy Participants

This study will assess the effect of multiple doses of AZD5462 on the PK of oral midazolam (CYP3A4 probe), rosuvastatin (OATP1B1/3, BCRP probe), and digoxin (P-gp probe) in healthy participants.

This study will consist of 2 treatment arms (Treatment Arms A and B) and within each treatment arm, the participants will first be administered the probe substrates (midazolam, rosuvastatin, and digoxin) alone followed by administration of the probe substrates together with AZD5462. The treatment arms differ in the dose of AZD5462 being administered and will be performed sequentially starting with Treatment Arm A (AZD5462 Dose A, high dose treatment arm) and followed by Treatment Arm B (AZD5462 Dose B, low dose treatment arm). Each treatment arm will include 5 periods.

Read more

Thirty two participants in total (16 participants per treatment arm) will be enrolled to ensure at least 24 evaluable participants (12 participants per treatment arm) at the end of the last treatment period.

A follow-up visit at Day 24 (+-1 Day) will be conducted via a phone call.

Read the detailed description

This is a phase I, single-centre, 2-treatment arm, 5-period, fixed sequence study.

The Study Will Comprise of a Screening Period and Five Treatment Periods:

  • Screening Period (Maximum 28 Days) Participant eligibility will be confirmed during the Screening Visit.
  • Period 1 (Day 1) Single dose administration of midazolam on Day 1.
  • Period 2 (Day 2) Single dose administration of rosuvastatin and digoxin on Day 2. There will be a minimum washout period of 3 days between Period 2 and Period 3.
  • Period 3 (Days 6 to 14) Single dose administration of rosuvastatin and digoxin together with AZD5462 (Treatment Arm A, Dose A; Treatment Arm B, Dose B) on Day 6. AZD5462 will continue to be administered throughout the period including Day 14.
  • Period 4 (Day 15) Single dose administration of midazolam together with AZD5462 (Treatment Arm A, Dose A; Treatment Arm B, Dose B) at steady state on Day 15.
  • Period 5 (Days 16 to 18) Single dose administration of rosuvastatin and digoxin together with AZD5462 (Treatment Arm A, Dose A; Treatment Arm B, Dose B) at steady state on Day 16. AZD5462 will continue to be administered on Days 17 and 18.

Participants will be resident in the study centre when dosed with probe substrates (midazolam, rosuvastatin, and digoxin) and/or AZD5462 including the washout period between Period 2 and Period 3. Residency will commence on Day -1 and end on Day 20.

A follow-up visit at Day 24 (+-1 Day) will be conducted via a phone call.

Being tested
AZD5462, Midazolam, Rosuvastatin, Digoxin
Keywords
Cytochrome P450 enzyme 3A4, Organic Anion Transporting Polypeptide 1B1/1B3, Breast Cancer Resistance Protein, P-glycoprotein

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD5462Drug

    Treatment Arm A: Participants will receive the IMP, AZD5462 Dose A starting on Day 6 and continued until Day 18 and the following approved medicinal products:

    • Midazolam
    • Rosuvastatin
    • Digoxin

    Treatment Arm B: Participants will receive the IMP, AZD5462 Dose B starting on Day 6 and continued until Day 18 and the following approved medicinal products:

    • Midazolam
    • Rosuvastatin
    • Digoxin
  • MidazolamDrug

    Participants will receive a single dose of midazolam in the morning of Day 1 and in the morning of Day 15 in both the arms.

  • RosuvastatinDrug

    Participants will receive rosuvastatin as a single dose administered with digoxin at the same time in the morning of Day 2, Day 6, and in the morning of Day 16 in both the arms.

  • DigoxinDrug

    Participants will receive digoxin as a single dose administered with rosuvastatin at the same time in the morning of Day 2, Day 6, and in the morning of Day 16 in both the arms.

Study groups in NCT05395117
Study groupRoleWhat they receive
Treatment Arm A: High doseExperimentalParticipants will receive the Investigational Medicinal Product (IMP), AZD5462 Dose A starting on Day 6 and continued until Day 18 and the following approved medicinal products: * Midazolam * Rosuvastatin * Digoxin
Receives: Drug: AZD5462; Drug: Midazolam; Drug: Rosuvastatin; Drug: Digoxin
Treatment Arm B: Low doseExperimentalParticipants will receive the IMP, AZD5462 Dose B starting on Day 6 and continued until Day 18 and the following approved medicinal products: * Midazolam * Rosuvastatin * Digoxin
Receives: Drug: AZD5462; Drug: Midazolam; Drug: Rosuvastatin; Drug: Digoxin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area under the concentration-versus-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf)

    The effect of AZD5462 on the AUCinf of oral midazolam, rosuvastatin, and digoxin will be assessed.

    Measured: Midazolam: Period 1 (Day 1), and Period 4 (Day 15); Rosuvastatin and Digoxin: Period 2 (Day 2), Period 3 (Days 6 - 14), and Period 5 (Days 16 - 18)

  2. Area under the concentration-versus-time curve from pre-dose (time 0) to the time of the last quantifiable concentration (AUClast)

    The effect of AZD5462 on the AUClast of oral midazolam, rosuvastatin, and digoxin will be assessed.

    Measured: Midazolam: Period 1 (Day 1), and Period 4 (Day 15); Rosuvastatin and Digoxin: Period 2 (Day 2), Period 3 (Days 6 - 14), and Period 5 (Days 16 - 18)

  3. Maximum observed serum (peak) drug concentration [Cmax]

    The effect of AZD5462 on the Cmax of oral midazolam, rosuvastatin, and digoxin will be assessed.

    Measured: Midazolam: Period 1 (Day 1), and Period 4 (Day 15); Rosuvastatin and Digoxin: Period 2 (Day 2), Period 3 (Days 6 - 14), and Period 5 (Days 16 - 18)

Secondary outcomes (7)
  1. Time to reach peak or maximum observed concentration or response following drug administration (tmax)

    The effect of AZD5462 on the tmax of oral midazolam, rosuvastatin, and digoxin will be assessed.

    Measured: Midazolam: Period 1 (Day 1), and Period 4 (Day 15); Rosuvastatin and Digoxin: Period 2 (Day 2), Period 3 (Days 6 - 14), and Period 5 (Days 16 - 18)

  2. Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t1/2λz)

    The effect of AZD5462 on the t1/2λz of oral midazolam, rosuvastatin, and digoxin will be assessed.

    Measured: Midazolam: Period 1 (Day 1), and Period 4 (Day 15); Rosuvastatin and Digoxin: Period 2 (Day 2), Period 3 (Days 6 - 14), and Period 5 (Days 16 - 18)

  3. Partial area under the serum concentration time curve from time 0 to time 12 (AUC0-12h)

    The AUC0-12h of AZD5462 will be determined.

    Measured: Day 6, and Day 16

  4. Maximum observed serum (peak) drug concentration [Cmax]

    The Cmax of AZD5462 will be determined.

    Measured: Day 6, and Day 16

  5. Time to reach peak or maximum observed concentration or response following drug administration (tmax)

    The tmax of AZD5462 will be determined.

    Measured: Day 6, and Day 16

  6. Trough plasma exposure of AZD5462 (Ctrough)

    Ctrough values of AZD5462 will be determined.

    Measured: Days 14 to 15, and Days 17 to 18

  7. Incidence of Adverse Events (AEs)

    The safety and tolerability of AZD5462 alone and in combination with midazolam, rosuvastatin, and digoxin will be examined.

    Measured: From screening (Day -28 to Day -2) to follow-up (Day 20)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2022
  2. Study start30 Jun 2022
  3. Primary completion12 Sep 2022
  4. Study completion12 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05395117
Sponsor's protocol ID
D9090C00003
Status last verified
Dec 2023
First submitted
24 May 2022
Last updated
13 Dec 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD5462, Midazolam and Rosuvastatin in people with Healthy Participants, run by AstraZeneca at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area under the concentration-versus-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf) (time frame: Midazolam: Period 1 (Day 1), and Period 4 (Day 15); Rosuvastatin and Digoxin: Period 2 (Day 2), Period 3 (Days 6 - 14), and Period 5 (Days 16 - 18)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2023.

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