A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of AZD9567.
NCT ID: NCT02760316
Last Updated: 2017-10-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
64 participants
INTERVENTIONAL
2016-05-02
2017-09-11
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The study is planned to have 6 cohorts with the option to include up to two additional cohorts if deemed necessary. Nine subjects participated in the first cohort (7 subjects randomised to receive AZD9567 and 2 subjects randomised to receive prednisolone 20 mg)and eleven subjects will participate in subsequent 3 cohorts (7 subjects will be randomised to receive AZD9567 and 4 subjects randomised to receive prednisolone 20 mg). A cohort 5 was included in the study in version 4.0 of the CSP. In this cohort two doses of prednisolone was tested, 5 mg and 20 mg. Up to six dose levels of AZD9567 are planned to be tested in the study and an additional cohort will be used in case any previous dose needs to be repeated or a new lower dose explored (ref CSP 5.0).
Therefore a maximum of 95 individuals could be included in the study (as stated in version 5.0 of this protocol). Subjects will be dosed for 5 consecutive days and a follow-up visit will occur 10-14 days after the last dose.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
AZD9567 oral suspension of 10 mg
Participants will receive oral supension of 10 mg dose strength
AZD9567 10 mg
Oral suspension Multiple doses 5 days of treatment Once daily
AZD9567 oral suspension of 20 mg
Participants will receive oral suspension of 20 mg dose strength
AZD9567 20 mg
Oral suspension Multiple doses 5 days of treatment Once daily
AZD9567 oral suspension of 40 mg
Participants will receive oral suspension of 40 mg dose strength
AZD9567 40 mg
Oral suspension Multiple doses 5 days of treatment Once daily
AZD9567 oral suspension of 80 mg
Participants will receive oral suspension of 80mg dose strength
AZD9567 80 mg
Oral suspension Multiple doses 5 days of treatment Once daily
Prednisolone oral capsules of 20 mg
Participants will receive oral capsules of 5 mg dose strength
Prednisolone 20 mg
Oral Multiple doses 5 days of treatment Once daily
AZD9567 oral suspension of 125 mg
Participants will receive oral suspension of 125 mg dose strength
AZD9567 125 mg
Oral Multiple doses 5 days of treatment Once daily
AZD9567 oral suspension of 155 mg
Participants will receive oral suspension of 155 mg dose strength
AZD9567 155 mg
Oral Multiple doses 5 days of treatment Once daily
Prednisolone oral capsules of 5 mg
Participants will receive oral capsules of 5 mg dose strength
Prednisolone 5 mg
Oral Multiple doses 5 days of treatment Once daily
Prednisolone oral capsules of 40 mg
Participants will receive oral capsules of 5 mg dose strength
Prednisolone 40 mg
Oral Multiple doses 5 days of treatment Once daily
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
AZD9567 10 mg
Oral suspension Multiple doses 5 days of treatment Once daily
AZD9567 20 mg
Oral suspension Multiple doses 5 days of treatment Once daily
AZD9567 40 mg
Oral suspension Multiple doses 5 days of treatment Once daily
AZD9567 80 mg
Oral suspension Multiple doses 5 days of treatment Once daily
Prednisolone 20 mg
Oral Multiple doses 5 days of treatment Once daily
AZD9567 125 mg
Oral Multiple doses 5 days of treatment Once daily
AZD9567 155 mg
Oral Multiple doses 5 days of treatment Once daily
Prednisolone 5 mg
Oral Multiple doses 5 days of treatment Once daily
Prednisolone 40 mg
Oral Multiple doses 5 days of treatment Once daily
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
3. Serum cortisol levels within normal limits at Screening (collected as part of the clinical chemistry panel) at the discretion of the Investigator.
4. Able to understand, read and speak the language of the ICD approved by the EC/IRB
5. Provision of signed and dated, written informed consent prior to any study specific procedures.
Exclusion Criteria
2. History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
3. History or presence of dyspepsia or oral intolerance to steroids.
4. History of or active or latent tuberculosis (TB), or at risk for having acquired TB (social workers or prison staff in countries with endemic rates of TB, having lived with patients with known TB).
5. History suggesting abnormal immune function, as judged by the Investigator.
6. History of severe affective disorder including depressive or maniac-depressive illness.
7. History of previous steroid psychosis
8. Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
9. Any latent or chronic infections or at risk of infection, or history of skin abscesses within 90 days prior to the first administration of IMP at the discretion of the Investigator.
10. Any clinically important laboratory abnormalities (serum biochemistry, hematology, coagulation or urinalysis results) at Screening or prior to randomisation, as judged by the Investigator. Explanatory note: In particular a subject with an abnormal value (2x upper level of normal) for alkaline phosphatase (ALP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST), serum creatinine (1.2x upper level of normal), and/or above the upper level of normal in serum bilirubin, or with an abnormal value for haemoglobin (Hb), white blood cell (WBC) and/or absolute neutrophil count below the normal limit will be excluded.
11. Any positive result at Screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and/or human immunodeficiency virus (HIV).
12. Abnormal vital signs after 10 minutes supine rest.
Explanatory note: Deviations from normal vital signs within the following ranges will not be allowed as any of the following:
* Systolic BP (SBP) \< 90mmHg or \> 140 mmHg
* Diastolic BP (DBP) \< 50mmHg or \> 90 mmHg
* Heart rate \< 50 or \> 90 beats per minute (bpm)
13. Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and 12-lead ECG that may interfere with the interpretation of QTc changes Explanatory note: this also includes abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
14. Prolonged QTcF \> 450 ms or family history of long QT syndrome.
15. PR(PQ) interval shortening \< 120 ms (PR \> 110 ms but \< 120 ms is acceptable if there is no evidence of ventricular pre-excitation).
16. PR (PQ) interval prolongation (\> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation.
17. Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS \> 110 ms.
Explanatory note: Subjects with QRS \> 110 ms but \< 115 ms are acceptable if there is no evidence of, for example, ventricular hypertrophy or pre-excitation.
18. Known or suspected history of drug abuse in the last 6 months, as judged by the Investigator.
19. Smokers that smoke ≥ 5 cigarettes/pipes per day, or use tobacco in any other form. Smoking will not be allowed during the study treatment period (Day -2 to Day 6) (1 e-cigarette = 1 cigarette).
20. History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
21. Positive screen for drugs of abuse or alcohol at Screening or on admission to the clinical unit.
22. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class to study drugs.
23. Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the Investigator.
24. Receipt of live or live attenuated vaccine within 4 weeks prior to the first administration of IMP.
25. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
26. Use of any prescribed or non-prescribed medication during the two weeks prior to the first administration of IMP or longer if the medication has a long half-life. Explanatory note: the prohibited medication includes antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals
27. Plasma donation within one month of screening or any blood donation/blood loss \> 500 mL during the 3 months prior to screening.
28. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months or 5 half-lifes, whatever is the longest of the first administration of IMP.
Explanatory note: the period of exclusion begins three months after the final dose or one month after the last visit whichever is the longest. Subjects consented and screened, but not randomised in this study or a previous phase I study, are not excluded.
29. Vulnerable subject, e.g., kept in detention, protected adult under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
30. Involvement of any Astra Zeneca or PAREXEL or study site employee or their close relatives.
31. Judgment by the Investigator that the subject should not participate in the study Explanatory note: for example, if the subject has any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data, or is considered unlikely to comply with study procedures, restrictions and requirements, the subject should not be randomised.
32. Subject who is a vegan or has medical dietary restrictions.
33. Subject who cannot communicate reliably with the Investigator/site staff.
18 Years
55 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
AstraZeneca
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Rainard Fuhr, Dr. med.
Role: PRINCIPAL_INVESTIGATOR
PAREXEL Early Phase Clinical Unit, Berlin
Pablo ForteSoto, Dr.
Role: PRINCIPAL_INVESTIGATOR
PAREXEL Early Phase Clinical Unit, London
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Research Site
Berlin, , Germany
Research Site
Harrow, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Hegelund Myrback T, Prothon S, Edman K, Leander J, Hashemi M, Dearman M, Edenro G, Svanberg P, Andersson EM, Almquist J, Ammala C, Hendrickx R, Taib Z, Johansson KA, Berggren AR, Keen CM, Eriksson UG, Fuhr R, Carlsson BCL. Effects of a selective glucocorticoid receptor modulator (AZD9567) versus prednisolone in healthy volunteers: two phase 1, single-blind, randomised controlled trials. Lancet Rheumatol. 2020 Jan;2(1):e31-e41. doi: 10.1016/S2665-9913(19)30103-1. Epub 2019 Dec 9.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
D6470C00002
Identifier Type: -
Identifier Source: org_study_id