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

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
  • 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.