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

NCT02760316 | Completed Phase 1

• 1 other identifier: D6470C00002
• Study Type: interventional
• Target: 64
• Locations: 2 countries
• Sites: 2

Brief Summary

A study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD9567.

Conditions

Rheumatoid Arthritis

Keywords

Healthy Volunteers; Obese; Insulin Resistant Subjects; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (5)

• Safety and tolerability: Adverse events (AEs)

  Adverse events will be summarized by each dose of AZD9567, pooled prednisolone 20 mg and pooled AZD9567 doses. Tabulations will include causality and severity (mild, moderate and severe), where applicable, and be presented by System Organ Class (SOC) and Preferred Term (PT) where applicable.

  Up to 5 days

• Safety and tolerability: Vital signs (blood pressure [BP], pulse rate, weight and oral body temperature)

  Descriptive statistics will be presented by treatment and time point for both observed values and changes from baseline, based on the safety analysis sets. The incidence of clinically notable vital sign abnormalities (vital signs outside the predefined criteria) will be summarized.

  Up to 5 days

• Safety and tolerability: Clinical laboratory safety evaluations (hematology, serum biochemistry [including S-cortisol and basal S-DHEAS], coagulation and urinalysis)

  Summary tabulations will be presented by treatment including observed values and changes from baseline. Shift tables will be presented to show the shifts from baseline to the minimum and maximum post-baseline measurements, respectively, by treatment, based on the safety analysis set.

  Up to 5 days

• Safety and tolerability: Electrocardiograms (12-lead dECGs, safety ECG's, and telemetry)

  Results of the safety ECGs, including normal/abnormal and specific findings will be listed for each subject.

  Up to 5 days

• Safety and tolerability: Physical examinations

  The results of the physical examination will be listed by body system for each subject.

  Up to 5 days

Secondary Outcomes (18)

• Pharmacokinetic parameter: Observed maximum concentration (Cmax)

  Up to 5 days

• Pharmacokinetic parameter: Area Under the curve from 0 to last quantifiable (AUC (0-last))

  Up to 5 days

• Pharmacokinetic parameter: Area Under the curve from 0 to 24h (AUC (0-24))

  Up to 5 days

• Pharmacokinetic parameter: Area Under the curve from 0 to infinity (AUC(0-inf))

  Up to 5 days

• Pharmacokinetic parameter: Area Under the curve from 0 to last quantifiable divided by the dose (AUC(0-last)/D)

  Up to 5 days

Study Arms (9)

AZD9567 oral suspension of 10 mg

EXPERIMENTAL

Participants will receive oral supension of 10 mg dose strength

Drug: AZD9567 10 mg

AZD9567 oral suspension of 20 mg

EXPERIMENTAL

Participants will receive oral suspension of 20 mg dose strength

Drug: AZD9567 20 mg

AZD9567 oral suspension of 40 mg

EXPERIMENTAL

Participants will receive oral suspension of 40 mg dose strength

Drug: AZD9567 40 mg

AZD9567 oral suspension of 80 mg

EXPERIMENTAL

Participants will receive oral suspension of 80mg dose strength

Drug: AZD9567 80 mg

Prednisolone oral capsules of 20 mg

ACTIVE COMPARATOR

Participants will receive oral capsules of 5 mg dose strength

Drug: Prednisolone 20 mg

AZD9567 oral suspension of 125 mg

EXPERIMENTAL

Participants will receive oral suspension of 125 mg dose strength

Drug: AZD9567 125 mg

AZD9567 oral suspension of 155 mg

EXPERIMENTAL

Participants will receive oral suspension of 155 mg dose strength

Drug: AZD9567 155 mg

Prednisolone oral capsules of 5 mg

ACTIVE COMPARATOR

Participants will receive oral capsules of 5 mg dose strength

Drug: Prednisolone 5 mg

Prednisolone oral capsules of 40 mg

ACTIVE COMPARATOR

Participants will receive oral capsules of 5 mg dose strength

Drug: Prednisolone 40 mg

Interventions

AZD9567 10 mg DRUG

Oral suspension Multiple doses 5 days of treatment Once daily

AZD9567 oral suspension of 10 mg

AZD9567 20 mg DRUG

Oral suspension Multiple doses 5 days of treatment Once daily

AZD9567 oral suspension of 20 mg

AZD9567 40 mg DRUG

Oral suspension Multiple doses 5 days of treatment Once daily

AZD9567 oral suspension of 40 mg

AZD9567 80 mg DRUG

Oral suspension Multiple doses 5 days of treatment Once daily

AZD9567 oral suspension of 80 mg

Prednisolone 20 mg DRUG

Oral Multiple doses 5 days of treatment Once daily

Prednisolone oral capsules of 20 mg

AZD9567 125 mg DRUG

Oral Multiple doses 5 days of treatment Once daily

AZD9567 oral suspension of 125 mg

AZD9567 155 mg DRUG

Oral Multiple doses 5 days of treatment Once daily

AZD9567 oral suspension of 155 mg

Prednisolone 5 mg DRUG

Oral Multiple doses 5 days of treatment Once daily

Prednisolone oral capsules of 5 mg

Prednisolone 40 mg DRUG

Oral Multiple doses 5 days of treatment Once daily

Prednisolone oral capsules of 40 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.
• Serum cortisol levels within normal limits at Screening (collected as part of the clinical chemistry panel) at the discretion of the Investigator.
• Able to understand, read and speak the language of the ICD approved by the EC/IRB
• Provision of signed and dated, written informed consent prior to any study specific procedures.

You may not qualify if:

• 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.
• 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.
• History or presence of dyspepsia or oral intolerance to steroids.
• 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).
• History suggesting abnormal immune function, as judged by the Investigator.
• History of severe affective disorder including depressive or maniac-depressive illness.
• History of previous steroid psychosis
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• 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.
• 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.
• Any positive result at Screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and/or human immunodeficiency virus (HIV).
• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Berlin, 14050, Germany

Location

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38258274 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid; Obesity

Interventions

AZD9567; Prednisolone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Rainard Fuhr, Dr. med.

  PAREXEL Early Phase Clinical Unit, Berlin

  PRINCIPAL INVESTIGATOR

• Pablo ForteSoto, Dr.

  PAREXEL Early Phase Clinical Unit, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2016
• First Posted: May 3, 2016
• Study Start: May 2, 2016
• Primary Completion: September 11, 2017
• Study Completion: September 11, 2017
• Last Updated: October 17, 2017

Record last verified: 2017-10

Locations

DE (1); GB (1)