AsthmaPhase 1NCT03140072

A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of AZD9898

A Phase 1 study testing AZD9898 in people with Asthma, run by AstraZeneca at 2 sites in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

In this integrated, multi-part, Phase I study, the safety, tolerability, food effect, pharmacokinetic (PK) and pharmacodynamic (PD) properties of single and repeated doses of AZD9898 will be investigated. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Asthma
What is being tested?: AZD9898
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 34 participants
Where: 2 sitesUnited Kingdom
Study dates: 10 May 2017to 23 Aug 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 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

For Parts 1 and 3:
Healthy male and female subjects aged 18 to 50 years.
All females must have a negative pregnancy test at the screening visit and on admission to the clinical unit, must not be lactating and must be of non-childbearing potential. • Has 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.
For Part 2:
In addition to the inclusion criteria for Parts 1 and 3, Male and female subjects aged 18 to 60 years.
Has been diagnosed by a physician with asthma for at least 12 months prior to the screening visit.
Has an FEV1 ≥ 65% at the screening visit and prior to dosing on Day 1, as measured before administration of a bronchodilator at both time points.
Has been on stable standard asthma treatment.

Who cannot join

For Parts 1,2,3:
History of any clinically important disease or disorder.
History of unstable psychiatric disorders.
History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with the drugs.
Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the screening visit or the first administration of IMP.
Any clinically important abnormalities in hematology, clinical chemistry or urinalysis results at the screening visit or on admission.

Show all 35Show fewer

Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV) type I and II antibodies.
Abnormal vital signs. Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG.
Prolonged QTcF > 450 ms or shortened QTcF < 340 ms.
PR (PQ) interval shortening. PR (PQ) interval prolongation.
Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS > 110 ms.
Subjects with QRS > 110 ms, but < 115 ms are acceptable if there is no evidence of, e.g., ventricular hypertrophy or pre-excitation.
Known or suspected history of drug abuse.
Current smokers or those who have smoked or used nicotine products within the previous 3 months.
History of alcohol abuse.
Positive testing for drugs of abuse or alcohol or cotinine at the screening visit or on admission.
History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
Excessive intake of caffeine-containing drinks or food.
Use of drugs with enzyme inducing properties.
Apart from use of required asthma medication, use of any other 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.
Use of any prescribed or non-prescribed leukotriene modifiers (e.g., montelukast) within 3 months prior to administration of IMP.
Hormone replacement therapy is not allowed for females, in order to exclude any drug-drug interaction.
Plasma donation within one month of the screening visit or any blood donation/blood loss exceeding 500 mL during the 3 months prior to the screening visit.
Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study.
Subjects who have previously received AZD9898.
Involvement of any AstraZeneca or study center employee or their close relatives.
Judgment by the Investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data.
Subjects who are vegans or have medical dietary restrictions (only applicable for volunteers participating in the food effect cohort in Part 3 of the study).
Subjects who cannot communicate reliably with the Investigator.
Vulnerable subjects.
Male subjects with a female partner already pregnant at the time of the screening visit will be excluded from the study.
Previous bone marrow transplant. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
For part 2:
If SABAs are used, serum or plasma potassium levels must be within the normal range and not lower than 3.8 mEq/L at the screening visit and on admission.
Meet any of the standard Hy's Law criteria at the screening visit or on admission.

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

Research Site
Harrow, HA1 3UJ
Research Site
Manchester, M23 9QZ

Other trials in United Kingdom

About this study

Official title: A Phase I, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of Single and Multiple Ascending Oral Doses of AZD9898 in Healthy Volunteers and Asthma Patients.

Read the detailed description

This study will be a Phase I, randomized, placebo-controlled study in healthy subjects and asthma patients, performed at 2 study centers. The study will consist of 3 parts (Part 1 [SAD in healthy subjects]; Part 2 [SAD in asthma patients]; Part 3 [MAD in healthy subjects under fasted conditions, with one cohort participating under fed conditions during one day as well]). The SAD cohorts in Parts 1 and 2 of the study will include male and women of non-childbearing potential (WONCBP) until the exposure limit for males has been reached. If an additional cohort for Parts 1 and 2 with a dose exceeding exposure limits in males is warranted (to explore the upper end of the dose response curve), this will be conducted in WONCBP only. Cohorts in Part 3 will include male subjects and WONCBP, depending on recruitment feasibility. All cohorts in the study will be single-blinded.

Conditions: Asthma
Being tested: AZD9898, Matching Placebo
Keywords: Asthma, Single Ascending Dose (SAD), Multiple Ascending Dose (MAD), AZD9898
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD9898Drug
In Parts 1 and 2 of the study, each subject/patient will receive a single dose (one dose level) of AZD9898, under fasted conditions. Starting dose in part 1 (SAD in healthy subjects) is 3 mg, subsequent doses will be selected based on emerging data. In Part 3 of the study, each subject will receive one dose level of AZD9898, once daily, under fasted or fed conditions. Subjects participating in Part 3B (food effect cohort) will receive an additional administration of the same dose, on the last day to investigate the effects of food.
Matching PlaceboDrug
In Parts 1 and 2 of the study, each subject/patient will receive a single dose (one dose level) of matching placebo, under fasted conditions. In Part 3 of the study, each subject will receive one dose level of matching placebo, once daily, under fasted or fed conditions. Subjects participating in Part 3B (food effect cohort) will receive an additional administration of the same dose, on the last day to investigate the effects of food.

Study groups in NCT03140072
Study group	Role	What they receive
AZD9898	Experimental	In Part 1 of the study, 5 single dose cohorts are planned to be evaluated, where AZD9898 will be administered. Eight subjects will participate in each cohort. Within each cohort, 6 (alternatively 8 or 10) subjects will be randomized to receive a single dose of AZD9898. Fifteen asthma patients are planned to participate in 3 cohorts in Part 2. Five patients will participate in each cohort. Within each cohort, 4 (alternatively 6 or 8) patients will be randomized to receive a single dose of AZD9898. In Part 3, 3 dose cohorts are planned. Nine healthy subjects will participate in each cohort. Within each cohort, 6 (alternatively 8, 10 or 12) subjects will be randomized to receive AZD9898. The subjects taking part in one of the MAD cohorts under fasted conditions will also take part in Part 3B in order to explore the influence of food on the PK of AZD9898. Receives: Drug: AZD9898
Placebo	Placebo comparator	In Part 1 of the study, 5 single dose cohorts are planned to be evaluated, where matching placebo will be administered. Eight subjects will participate in each cohort. Within each cohort, 2 (alternatively 3) subjects will be randomized to receive a single dose of matching placebo. Fifteen asthma patients are planned to participate in 3 cohorts in Part 2. Five patients will participate in each cohort. Within each cohort, one patient (alternatively 2 or 3 patients) will be randomized to receive a single dose of matching placebo. In Part 3, 3 dose cohorts are planned. Nine healthy subjects will participate in each cohort. Within each cohort, 3 (alternatively 4) subjects will be randomized to receive matching placebo. Receives: Drug: Matching Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of patients with Adverse Events (AEs)
To assess the adverse events as a criteria of safety and tolerability variables.
Measured: Change from baseline up to follow-up (7-10 days after last dose)
Vital sign (Blood pressure [BP])
To assess the vital signs as a criteria of safety and tolerability variables.
Measured: Change from baseline up to follow-up (7-10 days after last dose)
Vital sign (pulse)
To assess the vital sign as a criteria of safety and tolerability variables.
Measured: Change from baseline up to follow-up (7-10 days after last dose)
Vital sign (temperature)
To assess the vital sign as a criteria of safety and tolerability variables.
Measured: Change from baseline up to follow-up (7-10 days after last dose)
Resting and digital electrocardiograms (ECGs)
To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.
Measured: Change from baseline up to follow-up (7-10 days after last dose)
Cardiac telemetry
To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.
Measured: Change from baseline up to Post-dose (at least 30 minutes pre-dose until at least 24 hours post-dose)
Physical examination
To assess the physical conditions as a criteria of safety and tolerability variables.
Measured: Change from baseline up to follow-up (7-10 days after last dose)
Laboratory assessments (hematology, clinical chemistry and urinalysis)
To assess hematology, clinical chemistry and urinalysis as a criteria of safety and tolerability variables.
Measured: Change from baseline up to follow-up (7-10 days after last dose)

Secondary outcomes (21)

PK assessment: Cmax (Observed maximum plasma concentration taken directly from the individual concentration-time curve)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: Days 1,2,3, For Part 3: Days 1, 2, 3,4, 5, 6 and up to Day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Ctrough (Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]))
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: tmax (Time to reach maximum plasma concentration, taken directly from the individual concentration-time curve)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: λz (Terminal rate constant, estimated by log-linear least-squares regression of the terminal part of the concentration-time curve)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: t1/2λz (Terminal half-life, estimated as (ln2)/λz)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: tlast (Time of last quantifiable plasma concentration)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC(0-last) (Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration, calculated by linear up/log down trapezoidal summation)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC (Area under the concentration-time curve in the plasma from zero (pre-dose) extrapolated to infinite time)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC(0-12) (Area under the plasma concentration-curve from time zero to 12 hours post-dose)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC(0-24) (Area under the plasma concentration-curve from time zero to 24 hours post-dose)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: CL/F (Apparent oral clearance estimated as dose divided by AUC)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: CLss/F (Apparent oral clearance at steady state)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: MRT (Mean residence time)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Vz/F (Apparent volume of distribution during terminal phase (extravascular administration))
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Vss/F (Apparent volume of distribution at steady state (extravascular administration))
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC(0-24)/D (Dose normalized AUC(0-24), estimated by dividing AUC(0-24) by the dose administered)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC/D (Dose normalized AUC, estimated by dividing AUC by the dose administered)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Cmax/D (Dose normalized Cmax, estimated by dividing Cmax by the dose administered)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Rac (Accumulation ratio)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: TCP (Time change parameter)
Evaluation of the PK of AZD9898 in Parts 1 (single ascending dose in healthy subjects), 2 (single ascending dose in asthma patients) and 3 (multiple ascending dose in healthy subjects) and multiple dose IMP administration under fed and fasted conditions in Part 3 of the study.
Measured: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PD Parameter: Plasma 4-β-hydroxy-cholesterol (Part 3 only)
The plasma 4-β-hydroxy-cholesterol at baseline versus after treatment will be evaluated.
Measured: Day -1 and last dosing day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 May 201723 Aug 2017

First posted4 May 2017
Study start10 May 2017
Primary completion23 Aug 2017
Study completion23 Aug 2017

Why it stopped: Terminated based on interim review

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for AsthmaStudies 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: Care provider
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03140072
Sponsor's protocol ID: D7620C00001
Status last verified: Jan 2018
First submitted: 28 Apr 2017
Last updated: 17 Jan 2018
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of Single and Multiple Ascending Oral Doses of AZD9898 in Healthy Volunteers and Asthma Patients.
ClinicalTrials.gov ID: NCT03140072
Acronym / sponsor ID: D7620C00001
Conditions: Asthma
Keywords: Asthma, Single Ascending Dose (SAD), Multiple Ascending Dose (MAD), AZD9898
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Terminated based on interim review
Enrolment: 34 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Parexel
Study start: 10 May 2017 (actual)
Primary completion: 23 Aug 2017 (actual)
Study completion: 23 Aug 2017 (actual)
First posted: 4 May 2017 (actual)
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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (care provider)
Number of arms: 2

Arm	Type	Receives
AZD9898	Experimental	Drug: AZD9898In Part 1 of the study, 5 single dose cohorts are planned to be evaluated, where AZD9898 will be administered. Eight subjects will participate in each cohort. Within each cohort, 6 (alternatively 8 or 10) subjects will be randomized to receive a single dose of AZD9898. Fifteen asthma patients are planned to participate in 3 cohorts in Part 2. Five patients will participate in each cohort. Within each cohort, 4 (alternatively 6 or 8) patients will be randomized to receive a single dose of AZD9898. In Part 3, 3 dose cohorts are planned. Nine healthy subjects will participate in each cohort. Within each cohort, 6 (alternatively 8, 10 or 12) subjects will be randomized to receive AZD9898. The subjects taking part in one of the MAD cohorts under fasted conditions will also take part in Part 3B in order to explore the influence of food on the PK of AZD9898.
Placebo	Placebo comparator	Drug: Matching PlaceboIn Part 1 of the study, 5 single dose cohorts are planned to be evaluated, where matching placebo will be administered. Eight subjects will participate in each cohort. Within each cohort, 2 (alternatively 3) subjects will be randomized to receive a single dose of matching placebo. Fifteen asthma patients are planned to participate in 3 cohorts in Part 2. Five patients will participate in each cohort. Within each cohort, one patient (alternatively 2 or 3 patients) will be randomized to receive a single dose of matching placebo. In Part 3, 3 dose cohorts are planned. Nine healthy subjects will participate in each cohort. Within each cohort, 3 (alternatively 4) subjects will be randomized to receive matching placebo.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (8 listed)

For Parts 1 and 3:
In addition to the inclusion criteria for Parts 1 and 3, Male and female subjects aged 18 to 60 years.
Has been diagnosed by a physician with asthma for at least 12 months prior to the screening visit.
Has an FEV1 ≥ 65% at the screening visit and prior to dosing on Day 1, as measured before administration of a bronchodilator at both time points.
Has been on stable standard asthma treatment.

Key exclusion criteria (35 listed)

For Parts 1,2,3:
If SABAs are used, serum or plasma potassium levels must be within the normal range and not lower than 3.8 mEq/L at the screening visit and on admission.
Meet any of the standard Hy's Law criteria at the screening visit or on admission.

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
AZD9898In Parts 1 and 2 of the study, each subject/patient will receive a single dose (one dose level) of AZD9898, under fasted conditions. Starting dose in part 1 (SAD in healthy subjects) is 3 mg, subsequent doses will be selected based on emerging data. In Part 3 of the study, each subject will receive one dose level of AZD9898, once daily, under fasted or fed conditions. Subjects participating in Part 3B (food effect cohort) will receive an additional administration of the same dose, on the last day to investigate the effects of food.	Drug	AZD9898
Matching PlaceboIn Parts 1 and 2 of the study, each subject/patient will receive a single dose (one dose level) of matching placebo, under fasted conditions. In Part 3 of the study, each subject will receive one dose level of matching placebo, once daily, under fasted or fed conditions. Subjects participating in Part 3B (food effect cohort) will receive an additional administration of the same dose, on the last day to investigate the effects of food.	Drug	Placebo

Primary outcome

Number of patients with Adverse Events (AEs)
Time frame: Change from baseline up to follow-up (7-10 days after last dose)
To assess the adverse events as a criteria of safety and tolerability variables.
Vital sign (Blood pressure [BP])
Time frame: Change from baseline up to follow-up (7-10 days after last dose)
To assess the vital signs as a criteria of safety and tolerability variables.
Vital sign (pulse)
Time frame: Change from baseline up to follow-up (7-10 days after last dose)
To assess the vital sign as a criteria of safety and tolerability variables.
Vital sign (temperature)
Time frame: Change from baseline up to follow-up (7-10 days after last dose)
To assess the vital sign as a criteria of safety and tolerability variables.
Resting and digital electrocardiograms (ECGs)
Time frame: Change from baseline up to follow-up (7-10 days after last dose)
To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.
Cardiac telemetry
Time frame: Change from baseline up to Post-dose (at least 30 minutes pre-dose until at least 24 hours post-dose)
To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.
Physical examination
Time frame: Change from baseline up to follow-up (7-10 days after last dose)
To assess the physical conditions as a criteria of safety and tolerability variables.
Laboratory assessments (hematology, clinical chemistry and urinalysis)
Time frame: Change from baseline up to follow-up (7-10 days after last dose)
To assess hematology, clinical chemistry and urinalysis as a criteria of safety and tolerability variables.

21 secondary outcomes

PK assessment: Cmax (Observed maximum plasma concentration taken directly from the individual concentration-time curve)
Time frame: Parts 1,2: Days 1,2,3, For Part 3: Days 1, 2, 3,4, 5, 6 and up to Day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Ctrough (Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]))
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: tmax (Time to reach maximum plasma concentration, taken directly from the individual concentration-time curve)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: λz (Terminal rate constant, estimated by log-linear least-squares regression of the terminal part of the concentration-time curve)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: t1/2λz (Terminal half-life, estimated as (ln2)/λz)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: tlast (Time of last quantifiable plasma concentration)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC(0-last) (Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration, calculated by linear up/log down trapezoidal summation)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC (Area under the concentration-time curve in the plasma from zero (pre-dose) extrapolated to infinite time)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC(0-12) (Area under the plasma concentration-curve from time zero to 12 hours post-dose)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC(0-24) (Area under the plasma concentration-curve from time zero to 24 hours post-dose)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: CL/F (Apparent oral clearance estimated as dose divided by AUC)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: CLss/F (Apparent oral clearance at steady state)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: MRT (Mean residence time)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Vz/F (Apparent volume of distribution during terminal phase (extravascular administration))
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Vss/F (Apparent volume of distribution at steady state (extravascular administration))
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC(0-24)/D (Dose normalized AUC(0-24), estimated by dividing AUC(0-24) by the dose administered)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: AUC/D (Dose normalized AUC, estimated by dividing AUC by the dose administered)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Cmax/D (Dose normalized Cmax, estimated by dividing Cmax by the dose administered)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: Rac (Accumulation ratio)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PK assessment: TCP (Time change parameter)
Time frame: Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose
PD Parameter: Plasma 4-β-hydroxy-cholesterol (Part 3 only)
Time frame: Day -1 and last dosing day

Results and safety

The study was stopped early (reason given: Terminated based on interim review). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
Individual participant dataSharing planned: No

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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.

Muna Albayaty principal investigator

PAREXEL Early Phase Clinical Unit London

Dave Singh principal investigator

The Medicines Evaluation Unit

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD9898 in people with Asthma, run by AstraZeneca at 2 sites in United Kingdom.

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 8 inclusion and 35 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: stopped early, as of the sponsor's last update on 17 Jan 2018. 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 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: Terminated based on interim review). Results are not available in the source record.

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?

Number of patients with Adverse Events (AEs) (time frame: Change from baseline up to follow-up (7-10 days after last dose)). The study lists 8 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 NCT03140072.

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 Jan 2018.