Rheumatoid ArthritisPhase 1NCT02760316
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of AZD9567.
A Phase 1 study testing AZD9567 10 mg, AZD9567 20 mg and AZD9567 40 mg in people with Rheumatoid Arthritis, run by AstraZeneca at 2 sites in 2 countries.
Trial summary
A study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD9567. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- AZD9567 10 mg, AZD9567 20 mg and AZD9567 40 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 2 May 2016to 11 Sep 2017
- 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
- 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.
Who cannot join
- 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.
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- 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
- Heart rate < 50 or > 90 beats per minute (bpm)
- 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.
- Prolonged QTcF > 450 ms or family history of long QT syndrome.
- PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation).
- PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation.
- 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.
- Known or suspected history of drug abuse in the last 6 months, as judged by the Investigator.
- 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).
- History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
- Positive screen for drugs of abuse or alcohol at Screening or on admission to the clinical unit.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class to study drugs.
- Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the Investigator.
- Receipt of live or live attenuated vaccine within 4 weeks prior to the first administration of 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 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
- Plasma donation within one month of screening or any blood donation/blood loss > 500 mL during the 3 months prior to screening.
- 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.
- Vulnerable subject, e.g., kept in detention, protected adult under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- Involvement of any Astra Zeneca or PAREXEL or study site employee or their close relatives.
- 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.
- Subject who is a vegan or has medical dietary restrictions.
- Subject who cannot communicate reliably with the Investigator/site staff.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official 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
A study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD9567.
Read the detailed description
This is a phase 1, randomised, single-blind, multiple ascending dose, double-dummy sequential group study in healthy subjects .
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
- Rheumatoid Arthritis
- Being tested
- AZD9567 10 mg, AZD9567 20 mg, AZD9567 40 mg, AZD9567 80 mg, Prednisolone 20 mg
- Keywords
- Healthy Volunteers, Obese, Insulin Resistant Subjects, Rheumatoid Arthritis
- Medical subject headings
- Arthritis, Rheumatoid, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9567 10 mgDrug
Oral suspension Multiple doses 5 days of treatment Once daily
AZD9567 20 mgDrug
Oral suspension Multiple doses 5 days of treatment Once daily
AZD9567 40 mgDrug
Oral suspension Multiple doses 5 days of treatment Once daily
AZD9567 80 mgDrug
Oral suspension Multiple doses 5 days of treatment Once daily
Prednisolone 20 mgDrug
Oral Multiple doses 5 days of treatment Once daily
AZD9567 125 mgDrug
Oral Multiple doses 5 days of treatment Once daily
AZD9567 155 mgDrug
Oral Multiple doses 5 days of treatment Once daily
Prednisolone 5 mgDrug
Oral Multiple doses 5 days of treatment Once daily
Prednisolone 40 mgDrug
Oral Multiple doses 5 days of treatment Once daily
| Study group | Role | What they receive |
|---|---|---|
| AZD9567 oral suspension of 10 mg | Experimental | Participants will receive oral supension of 10 mg dose strength Receives: Drug: AZD9567 10 mg |
| AZD9567 oral suspension of 20 mg | Experimental | Participants will receive oral suspension of 20 mg dose strength Receives: Drug: AZD9567 20 mg |
| AZD9567 oral suspension of 40 mg | Experimental | Participants will receive oral suspension of 40 mg dose strength Receives: Drug: AZD9567 40 mg |
| AZD9567 oral suspension of 80 mg | Experimental | Participants will receive oral suspension of 80mg dose strength Receives: Drug: AZD9567 80 mg |
| Prednisolone oral capsules of 20 mg | Active comparator | Participants will receive oral capsules of 5 mg dose strength Receives: Drug: Prednisolone 20 mg |
| AZD9567 oral suspension of 125 mg | Experimental | Participants will receive oral suspension of 125 mg dose strength Receives: Drug: AZD9567 125 mg |
| AZD9567 oral suspension of 155 mg | Experimental | Participants will receive oral suspension of 155 mg dose strength Receives: Drug: AZD9567 155 mg |
| Prednisolone oral capsules of 5 mg | Active comparator | Participants will receive oral capsules of 5 mg dose strength Receives: Drug: Prednisolone 5 mg |
| Prednisolone oral capsules of 40 mg | Active comparator | Participants will receive oral capsules of 5 mg dose strength Receives: Drug: Prednisolone 40 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 5 days
Safety and tolerability: Physical examinations
The results of the physical examination will be listed by body system for each subject.
Measured: Up to 5 days
Secondary outcomes (18)
Pharmacokinetic parameter: Observed maximum concentration (Cmax)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Area Under the curve from 0 to last quantifiable (AUC (0-last))
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Area Under the curve from 0 to 24h (AUC (0-24))
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Area Under the curve from 0 to infinity (AUC(0-inf))
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Area Under the curve from 0 to last quantifiable divided by the dose (AUC(0-last)/D)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Area Under the curve from 0 to 24h divided by the dose (AUC(0-24)/D)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Area Under the curve from 0 to infinity divided by the dose (AUC/D)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Observed maximum concentration divided by the dose (Cmax/D)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Time to reach maximum concentration (tmax)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Terminal rate constant (λz)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Terminal half-life (t1/2)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Apparent clearance divided by AUC (CL/F)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Aparent volume of distribution estimated by dividing de apparent clearance (Vz/F)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: Average plasma concentration (Cav)
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacokinetic parameter: fluctuation index
Plasma concentrations, and plasma PK parameters will be summarized by dose level of AZD9567 using descriptive statistics (n, geometric mean, geometric coefficient of variation [CV%], arithmetic mean, arithmetic Standard Deviation (SD), minimum, median and maximum) based on the respective PK analysis sets.
Measured: Up to 5 days
Pharmacodynamic parameter: Plasma glucose measured by Oral Glucose Tolerance Test (OGTT)
Concentration data for the OGTT (plasma glucose) will be listed and summarized by treatment, visit and time point. Each of the plasma glucose AUC (total net and incremental) parameters (0 to 2 hours and 0 to 4 hours) will be listed and summarized (including changes from baseline for the AUC values, where the baseline is the AUC values measured on Day -1) by visit and treatment for the final clinical study report. In addition, the glucose ratio values by time point and their corresponding AUCs will also be summarized.
Measured: Up to 5 days
Pharmacodynamic parameter: Serum insulin measured by Oral Glucose Tolerance Test (OGTT)
Concentration data for the OGTT (serum insulin) will be listed and summarized by treatment, visit and time point. Each of the serum insulin AUC (total net and incremental) parameters (0 to 2 hours and 0 to 4 hours) will be listed and summarized (including changes from baseline for the AUC values, where the baseline is the AUC values measured on Day -1) by visit and treatment for the final clinical study report. In addition, the serum insulin ratio values by time point and their corresponding AUCs will also be summarized.
Measured: Up to 5 days
Pharmacodynamic parameter: Serum C-peptide measured by Oral Glucose Tolerance Test (OGTT)
Concentration data for the OGTT (serum C-peptide) will be listed and summarized by treatment, visit and time point. Each of the serum C-peptide AUC (total net and incremental) parameters (0 to 2 hours and 0 to 4 hours) will be listed and summarized (including changes from baseline for the AUC values, where the baseline is the AUC values measured on Day -1) by visit and treatment for the final clinical study report.
Measured: Up to 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2016 (estimated)
- Study start2 May 2016
- Primary completion11 Sep 2017
- Study completion11 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rainard Fuhr, Dr. med., Principal investigator, PAREXEL Early Phase Clinical Unit, BerlinPablo ForteSoto, Dr., Principal investigator, PAREXEL Early Phase Clinical Unit, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02760316
- Sponsor's protocol ID
- D6470C00002
- Status last verified
- Oct 2017
- First submitted
- 25 Apr 2016
- Last updated
- 17 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38258274
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02760316
- Acronym / sponsor ID
- D6470C00002
- Conditions
- Rheumatoid Arthritis
- Keywords
- Healthy Volunteers, Obese, Insulin Resistant Subjects, Rheumatoid Arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 2 May 2016 (actual)
- Primary completion
- 11 Sep 2017 (actual)
- Study completion
- 11 Sep 2017 (actual)
- First posted
- 3 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD9567.
Detailed description
This is a phase 1, randomised, single-blind, multiple ascending dose, double-dummy sequential group study in healthy subjects .
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| AZD9567 oral suspension of 10 mg | Experimental | Drug: AZD9567 10 mgParticipants will receive oral supension of 10 mg dose strength |
| AZD9567 oral suspension of 20 mg | Experimental | Drug: AZD9567 20 mgParticipants will receive oral suspension of 20 mg dose strength |
| AZD9567 oral suspension of 40 mg | Experimental | Drug: AZD9567 40 mgParticipants will receive oral suspension of 40 mg dose strength |
| AZD9567 oral suspension of 80 mg | Experimental | Drug: AZD9567 80 mgParticipants will receive oral suspension of 80mg dose strength |
| Prednisolone oral capsules of 20 mg | Active comparator | Drug: Prednisolone 20 mgParticipants will receive oral capsules of 5 mg dose strength |
| AZD9567 oral suspension of 125 mg | Experimental | Drug: AZD9567 125 mgParticipants will receive oral suspension of 125 mg dose strength |
| AZD9567 oral suspension of 155 mg | Experimental | Drug: AZD9567 155 mgParticipants will receive oral suspension of 155 mg dose strength |
| Prednisolone oral capsules of 5 mg | Active comparator | Drug: Prednisolone 5 mgParticipants will receive oral capsules of 5 mg dose strength |
| Prednisolone oral capsules of 40 mg | Active comparator | Drug: Prednisolone 40 mgParticipants will receive oral capsules of 5 mg dose strength |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (39 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD9567 10 mgOral suspension Multiple doses 5 days of treatment Once daily | Drug | AZD9567 oral suspension of 10 mg |
| AZD9567 20 mgOral suspension Multiple doses 5 days of treatment Once daily | Drug | AZD9567 oral suspension of 20 mg |
| AZD9567 40 mgOral suspension Multiple doses 5 days of treatment Once daily | Drug | AZD9567 oral suspension of 40 mg |
| AZD9567 80 mgOral suspension Multiple doses 5 days of treatment Once daily | Drug | AZD9567 oral suspension of 80 mg |
| Prednisolone 20 mgOral Multiple doses 5 days of treatment Once daily | Drug | Prednisolone oral capsules of 20 mg |
| AZD9567 125 mgOral Multiple doses 5 days of treatment Once daily | Drug | AZD9567 oral suspension of 125 mg |
| AZD9567 155 mgOral Multiple doses 5 days of treatment Once daily | Drug | AZD9567 oral suspension of 155 mg |
| Prednisolone 5 mgOral Multiple doses 5 days of treatment Once daily | Drug | Prednisolone oral capsules of 5 mg |
| Prednisolone 40 mgOral Multiple doses 5 days of treatment Once daily | Drug | Prednisolone oral capsules of 40 mg |
Primary outcome
Safety and tolerability: Adverse events (AEs)
Time frame: Up to 5 days
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.
Safety and tolerability: Vital signs (blood pressure [BP], pulse rate, weight and oral body temperature)
Time frame: Up to 5 days
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.
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
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.
Safety and tolerability: Electrocardiograms (12-lead dECGs, safety ECG's, and telemetry)
Time frame: Up to 5 days
Results of the safety ECGs, including normal/abnormal and specific findings will be listed for each subject.
Safety and tolerability: Physical examinations
Time frame: Up to 5 days
The results of the physical examination will be listed by body system for each subject.
18 secondary outcomes
Pharmacokinetic parameter: Observed maximum concentration (Cmax)
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: 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 infinity (AUC(0-inf))
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: 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: Observed maximum concentration divided by the dose (Cmax/D)
Time frame: Up to 5 days
Pharmacokinetic parameter: Time to reach maximum concentration (tmax)
Time frame: Up to 5 days
Pharmacokinetic parameter: Terminal rate constant (λz)
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: Aparent volume of distribution estimated by dividing de apparent clearance (Vz/F)
Time frame: Up to 5 days
Pharmacokinetic parameter: Average plasma concentration (Cav)
Time frame: Up to 5 days
Pharmacokinetic parameter: fluctuation index
Time frame: Up to 5 days
Pharmacodynamic parameter: Plasma glucose measured by Oral Glucose Tolerance Test (OGTT)
Time frame: Up to 5 days
Pharmacodynamic parameter: Serum insulin measured by Oral Glucose Tolerance Test (OGTT)
Time frame: Up to 5 days
Pharmacodynamic parameter: Serum C-peptide measured by Oral Glucose Tolerance Test (OGTT)
Time frame: Up to 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2017.
- Derived from this study: PubMed 38258274Hegelund 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainard Fuhr, Dr. med. principal investigator
PAREXEL Early Phase Clinical Unit, Berlin
Pablo ForteSoto, Dr. principal investigator
PAREXEL Early Phase Clinical Unit, London
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD9567 10 mg, AZD9567 20 mg and AZD9567 40 mg in people with Rheumatoid Arthritis, run by AstraZeneca at 2 sites in 2 countries.
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 39 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 17 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, United Kingdom. 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?
Safety and tolerability: Adverse events (AEs) (time frame: Up to 5 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02760316, which also lists 1 linked publication.
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 17 Oct 2017.