A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of AZD9567.

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02760316
• Date of registration: 25/04/2016
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of AZD9567.
• Scientific title: A Phase I, Randomised, Single-blind Study to Asses the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of AZD9567 in Healthy Volunteers Using Prednisolone as Positive Control
• Date of first enrolment: May 2, 2016
• Target sample size: 64
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02760316
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Participant).
• Phase: Phase 1

Countries of recruitment

Germany, United Kingdom

Contacts

• Name: Pablo ForteSoto, Dr.
• Affiliation: PAREXEL Early Phase Clinical Unit, London

• Name: Rainard Fuhr, Dr. med.
• Affiliation: PAREXEL Early Phase Clinical Unit, Berlin

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or non-childbearing potential female subject, aged 18 to 55 years (both
inclusive) with suitable veins for cannulation or repeated venipuncture. Explanatory
note: Female subjects must be of non-childbearing potential, confirmed at screening by
fulfilling study predefined 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:

1. History of any clinically important disorder which, in opinion of the Investigator,
may either put the subject at risk or influence the results or the subject's ability
to participate in the study.

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


Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: AZD9567 20 mg

Drug: Prednisolone 40 mg

Drug: AZD9567 10 mg

Drug: Prednisolone 20 mg

Drug: AZD9567 80 mg

Drug: AZD9567 125 mg

Drug: AZD9567 155 mg

Drug: Prednisolone 5 mg

Drug: AZD9567 40 mg

Primary Outcome(s)

Safety and tolerability: Adverse events (AEs) [Time Frame: Up to 5 days]

Safety and tolerability: Vital signs (blood pressure [BP], pulse rate, weight and oral body temperature) [Time Frame: Up to 5 days]

Safety and tolerability: Clinical laboratory safety evaluations (hematology, serum biochemistry [including S-cortisol and basal S-DHEAS], coagulation and urinalysis) [Time Frame: Up to 5 days]

Safety and tolerability: Electrocardiograms (12-lead dECGs, safety ECG's, and telemetry) [Time Frame: Up to 5 days]

Safety and tolerability: Physical examinations [Time Frame: Up to 5 days]

Secondary Outcome(s)

Pharmacodynamic parameter: Serum C-peptide measured by Oral Glucose Tolerance Test (OGTT) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Area Under the curve from 0 to infinity (AUC(0-inf)) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Average plasma concentration (Cav) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Observed maximum concentration divided by the dose (Cmax/D) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: fluctuation index [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Observed maximum concentration (Cmax) [Time Frame: Up to 5 days]

Pharmacodynamic parameter: Plasma glucose measured by Oral Glucose Tolerance Test (OGTT) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Aparent volume of distribution estimated by dividing de apparent clearance (Vz/F) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Area Under the curve from 0 to 24h (AUC (0-24)) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Area Under the curve from 0 to 24h divided by the dose (AUC(0-24)/D) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Area Under the curve from 0 to infinity divided by the dose (AUC/D) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Area Under the curve from 0 to last quantifiable (AUC (0-last)) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Terminal rate constant (?z) [Time Frame: Up to 5 days]

Pharmacodynamic parameter: Serum insulin measured by Oral Glucose Tolerance Test (OGTT) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Area Under the curve from 0 to last quantifiable divided by the dose (AUC(0-last)/D) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Terminal half-life (t1/2) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Apparent clearance divided by AUC (CL/F) [Time Frame: Up to 5 days]

Pharmacokinetic parameter: Time to reach maximum concentration (tmax) [Time Frame: Up to 5 days]

Secondary ID(s)

D6470C00002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors