Single + Multiple Ascending Dose and Food Effect Study of AZD7986 in Healthy Volunteers, PK, PD and Safety Study

NCT ID: NCT02303574

Last Updated: 2018-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-03
• Study Completion Date: 2016-08-03

Brief Summary

This is a phase I, randomised, single-blind placebo-controlled, 2-part study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and food effect of single and multiple oral doses of AZD7986 in healthy volunteers

Conditions

Safety, Pharmacokinetics, Pharmacodynamics, Food Effect

Keywords

AZD7986, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Food Effect, First-in-human, Single Ascending Dose, Multiple Ascending Dose, Healthy Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

AZD7986, single and mulltiple doses

In Part 1 up to 8 cohorts with single doses starting with 5 mg AZD7986 as oral solution. In Part 2 up to 5 cohorts with multiple doses of AZD7986 as oral solution

Group Type: EXPERIMENTAL

AZD7986, oral solution, 1 to 50 mg/mL

Intervention Type: DRUG

Starting dose in single ascending dose part: 5 mg

Placebo, single and multiple doses

In Part 1 up to 8 cohorts and in Part 2 up to 5 cohorts with matching placebo to AZD7986 as oral solution

Group Type: PLACEBO_COMPARATOR

Placebo, oral solution

Intervention Type: DRUG

Matching placebo

Interventions

AZD7986, oral solution, 1 to 50 mg/mL

Starting dose in single ascending dose part: 5 mg

Intervention Type: DRUG

Placebo, oral solution

Matching placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated written informed consent prior to any study specific procedures.

2. Healthy male or female subjects aged 18 to 50 years (inclusive) at screening with suitable veins for cannulation or repeated venepuncture.

3. Females must be of non-child-bearing potential, confirmed at screening by fulfilling one of the following criteria:

• Post-menopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in the post menopausal range.
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

4. Male subjects must be non fertile, i.e., surgically sterilised with documentation of azoospermia or must practice an effective contraceptive method to prevent pregnancies. Effective contraceptive methods are:

• Sexual abstinence from before the first administration of the IMP until 3 months after final administration of the IMP, only if this is in line with the preferred and usual lifestyle of the subject.
• Use of a condom plus spermicide agent in addition to having their partner use another acceptable method (oral or injectable hormonal contraceptives, contraceptive patch, intrauterine devices, vaginal hormonal rings, vaginal diaphragm or cervical caps) from before the first administration of the IMP until 3 months after final administration of the IMP.
• Subject's sexual partner is of non childbearing potential, i.e., post menopausal or surgically sterilised (e.g., tubal ligation, hysterectomy in medical history).

5. Have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive at screening.

Exclusion Criteria

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Subject has increased risk of infection:

• History and/or presence of tuberculosis (TB); positive result for interferon gamma release assay (IGRA) (i.e., QuantiFERON TB-Gold), subjects who have resided in regions where tuberculosis and mycosis are endemic during 90 days before screening, or who intend to visit such a region during the duration of the study i.e. deserts areas, Eastern Europe, Central and South America, Africa except Egypt, Russia, Asia, Indonesia
• Oral body temperature of > 37.7°C on Day -1, or as judged by the Investigator.
• Blood neutrophil count < 1.7 x109/L (Screening and Day -1 morning sample).
• Is in high risk-group for HIV infection within the last 6 months (i.e., men who have had unprotected sex with men, women who have had sex without a condom with men who have sex with men, people who have had sex without a condom with a person who has lived or travelled in Africa, people who inject drugs, people who have had sex without a condom with somebody who has injected drugs, people who have caught another sexually transmitted infection, people who have received a blood transfusion while in Africa, eastern Europe, the countries of the former Soviet Union, Asia or central and southern America).
• Other latent or chronic infections (e.g., recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (surgery, trauma, or significant infection) within 90 days of screening, or history of skin abscesses within 90 days of screening.
• Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to screening, as determined by the Investigator.
• Volunteers with active malignancy or neoplastic disease in the previous 5 years other than superficial basal cell carcinoma.
• Disease history suggesting abnormal immune function.
• Volunteers who have received live or live-attenuated vaccine in the 4 weeks prior to dosing.
• High-sensitivity C-reactive protein above upper limit of laboratory reference range at screening and on Day -1.
• Some subjects lacking functional dipeptidyl peptidase 1 (DPP1) enzyme have been described to have periodontitis and palmoplantar hyperkeratosis:

• For Part 1a and Part 1b: Subjects with signs of current gingivitis/periodontitis. Gingival evaluation (by inspection) will be performed by a dental hygienist or trained study physician.
• For Part 2: Subjects with a history of recurring gingivitis/periodontitis or signs of current gingivitis/periodontitis. Gingival evaluation will be performed by a dental hygienist or trained study physician. Evaluation of bleeding propensity due to gingivitis will be performed by using dental hygienist instrumentation. Exact measurement of gum pockets is not needed.
• Subjects with a history of hyperkeratosis or erythema in palms or soles.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Annelize Koch, Dr

Role: PRINCIPAL_INVESTIGATOR

PAREXEL Early Phase Clinical Unit, Level 7, Northwick Park Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ, United Kingdom

Bengt Larsson

Role: STUDY_CHAIR

AstraZeneca

Locations

Research Site

Harrow, , United Kingdom

Countries

United Kingdom

Other Identifiers

2014-004043-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D6190C00001

Identifier Type: -

Identifier Source: org_study_id