A Study to Estimate the Effect of AZD5718 on the Pharmacokinetics (What Does the Body Does to the Drug) of Rosuvastatin to Measure the Relative Bioavailability (the Extent to Which a Drug or Other Substance Becomes Available to the Body) of AZD5718 Oral Suspension vs AZD5718 Immediate Release Tablet

NCT02963116 | Completed Phase 1

• 1 other identifier: D7550C00002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, open-label, 5-period, 5-treatment, single-dose, single-center, crossover study to estimate the effect of AZD5718 on the pharmacokinetics (PK) of rosuvastatin, and to assess the relative bioavailability of AZD5718 oral suspension vs AZD5718 immediate release (IR) Tablet Formulation and the Food Effect of AZD5718 in Healthy Volunteers. The study will be performed at a single study center.

Conditions

High Risk Coronary Artery Disease

Keywords

Pharmacokinetics (PK); Bioavailability (BA); Safety; Tolerability; Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• Area under plasma concentration-time curve from time zero to infinity (AUC) of Rosuvastatin

  Assessment of AUC of rosuvastatin when administered alone and in combination with AZD5718 in healthy volunteers.

  Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose

• Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-last)] of Rosuvastatin

  Assessment of AUC(0-last) of rosuvastatin when administered alone and in combination with AZD5718 in healthy volunteers.

  Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose

• Maximum observed plasma concentration (Cmax) of Rosuvastatin

  Assessment of Cmax of rosuvastatin when administered alone and in combination with AZD5718 in healthy volunteers.

  Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose

Secondary Outcomes (14)

• Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½) of Rosuvastatin -

  Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose. (Only Treatment A and B)

• Time to reach maximum observed plasma concentration (tmax) of rosuvastatin

  Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose. (Only Treatment A and B)

• AUC of AZD5718

  Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E)

• AUC(0-last) of AZD5718

  Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E)

• Cmax of AZD5718

  Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E)

Study Arms (5)

Treatment A

EXPERIMENTAL

10 mg rosuvastatin tablet alone (fasting state)

Drug: Rosuvastatin tablet

Treatment B

EXPERIMENTAL

10 mg rosuvastatin tablet + 200 mg of AZD5718 IR tablet (2 x 100 mg tablet) (fasting state)

Drug: AZD5718 IR tablet; Drug: Rosuvastatin tablet

Treatment C

EXPERIMENTAL

200 mg of AZD5718 IR tablet (2 x 100 mg tablet) (fasting state)

Drug: AZD5718 IR tablet

Treatment D

EXPERIMENTAL

200 mg of AZD5718 oral suspension 50 mg/mL (fasting state)

Drug: AZD5718 oral suspension

Treatment E

EXPERIMENTAL

200 mg of AZD5718 IR tablet (2 x 100 mg tablet) (fed state)

Drug: AZD5718 IR tablet

Interventions

AZD5718 IR tablet DRUG

Treatment B; Treatment C; Treatment E

AZD5718 oral suspension DRUG

Treatment D

Rosuvastatin tablet DRUG

Treatment A; Treatment B

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male and/or female subjects (of non childbearing potential) aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
• Females must have a negative pregnancy test at the Screening Visit and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria 3.1. Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone levels in the postmenopausal range.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral ophorectomy or bilateral salpingectomy but excluding bilateral tubal ligation.
• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg, inclusive.
• Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the subject at risk because of participation in the study, or influence the results or the subject'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 clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at the Screening Visit and/or admission to the study unit as judged by the PI including: - Aminotransferase (ALT) \> upper limit of normal (ULN); - Aspartate aminotransferase (AST) \> ULN; - Total bilirubin (TBL) \> ULN; and - Gamma glutamyl transpeptidase (GGT) \> ULN.
• Any clinically significant abnormal findings in vital signs at the Screening Visit and/or admission to the study unit, as judged by the PI defined as any of the following: - Systolic BP (SBP) \< 90 mmHg or ≥ 140 mmHg; - Diastolic BP (DBP) \< 50 mmHg or ≥ 90 mmHg; and - Pulse \< 45 or \> 85 beats per minute (bpm).
• Any clinically significant abnormalities (at the Screening Visit and admission) in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• Subjects with myopathy.
• Plasma donation within 1 month of the Screening Visit or any blood donation/loss more than 500 mL during the 3 months prior to the Screening Visit.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5718 and/or rosuvastatin.
• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to the Screening Visit.
• Positive screen for drugs of abuse or cotinine at the Screening Visit or on each admission to the study center or positive screen for alcohol on each admission to the study center.
• Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the investigator.
• 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 (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life. Note: Hormonal replacement therapy is not allowed for females.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

Related Publications (1)

• Ericsson H, Nelander K, Heijer M, Kjaer M, Lindstedt EL, Albayaty M, Forte P, Lagerstrom-Fermer M, Skrtic S. Phase 1 Pharmacokinetic Study of AZD5718 in Healthy Volunteers: Effects of Coadministration With Rosuvastatin, Formulation and Food on Oral Bioavailability. Clin Pharmacol Drug Dev. 2020 Apr;9(3):411-421. doi: 10.1002/cpdd.756. Epub 2019 Dec 2.

  PMID: 31793171 DERIVED

MeSH Terms

Interventions

Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dr. Muna Albayaty, MBChB, MSc, MFPM

  PAREXEL Early Phase Clinical Unit London

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 4, 2016
• First Posted: November 15, 2016
• Study Start: December 20, 2016
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: March 9, 2017

Record last verified: 2017-03

Locations

GB (1)