Healthy SubjectsPhase 1NCT02653872
A Phase I Study to Assess PK of AZD7986 Alone & With Verapamil, Itraconazole or Diltiazem in Healthy Subjects
A Phase 1 study testing AZD7986, Verapamil and Itraconazole in people with Healthy Subjects, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
This is a phase 1, non-randomized, fixed sequence, 3-period, drug-drug interaction study to assess the pharmacokinetics (PK) of AZD7986 in healthy subjects when administered alone and in combination with multiple doses of verapamil and itraconazole or diltiazem Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects
- What is being tested?
- AZD7986, Verapamil and Itraconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 22 Jan 2016to 13 Apr 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and/or female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venepuncture.
- Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:
- Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post menopausal range(> 40 milli-International unit [mIU]/mL).
- Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation.
- Have 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.
- Provision of signed, written and dated informed consent for optional genetic/biomarker research.
- Hormone replacement therapy is not allowed for females to exclude any drug drug interaction between the hormone replacement therapy and AZD7986.
Who cannot join
- 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 (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of AZD7986.
- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator.
- Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
- Any clinically significant abnormal findings in vital signs after at least 10 minutes of rest, defined as the following:
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- Systolic blood pressure < 100 mmHg or > 140 mmHg;
- Diastolic blood pressure < 50 mmHg or > 90 mmHg; or
- Pulse rate < 50 or > 85 beats per minute.
- Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 Lead ECG as considered by the investigator that may interfere with the interpretation of ECG interval measured from the onset of the QRS complex (electrical activity or ventricular contraction on the ECG where Q represents the downward deflection, R represents upward deflection and S represents a downward one) to the end of the T wave corrected for heart rate (QTc) interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
- Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 ms or shortened QTcF < 340 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 > 200 ms, intermittent second or third degree atrioventricular (AV) block (Wenckebach block while asleep is not exclusive), 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. 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, as judged by the investigator.
- Current smokers or those who have smoked or used nicotine products within the 3 months before screening.
- Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the investigator.
- Positive screen for drugs of abuse or cotinine at screening or on each admission to the study centre or positive screen for alcohol on each admission to the study unit.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD7986.
- Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate,) as judged by the investigator.
- Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of AZD7986.
- Use of any prescribed or non-prescribed medication including antacids and other drugs for gastric acid-related disorders, 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 AZD7986 or longer if the medication has a long half-life.
- Note: Hormonal replacement therapy is not allowed for females.
- Plasma donation within 1 month of screening or any blood donation/loss more than 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 of the first administration of AZD7986 in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest.
- Note: Subjects consented and screened, but not dosed in this study or a previous phase I study, are not excluded.
- Subjects who have previously received AZD7986.
- Involvement of any AstraZeneca, PAREXEL or study site 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 or are considered unlikely to comply with study procedures, restrictions, and requirements.
- Subjects who cannot communicate reliably with the investigator.
- Subjects who are vegans or have medical dietary restrictions.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- 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. The test may be repeated if the initial test result is indeterminate.
- 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.
- Subjects with active malignancy or neoplastic disease in the previous 5 years other than superficial basal cell carcinoma.
- Disease history suggesting abnormal immune function.
- Subjects 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.
- Subjects with a history or signs of current gingivitis/periodontitis or a history or current hyperkeratosis of palms and soles will be excluded. (Due to the fact that many subjects lacking functional DPP1 enzyme have been described to have periodontitis and palmoplantar hyperkeratosis.)
- Subjects with total urinary protein/urine creatinine ratio outside the normal range.
- Drugs affecting CYP3A4 should be refrained from use for 3 weeks prior to study commencement and thereafter until study completion.
- In addition, the following is considered a criterion for the exclusion from the optional genetic component of the study:
- History of bone marrow transplant
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
- Hypersensitivity to the verapamil or to any of the excipients.
- History of serious cardiac events such as myocardial infarction.
- History of sino-atrial block; sick sinus syndrome; chronic or uncompensated heart failure (including left ventricular heart failure).
- History of atrial flutter, atrial fibrillation or Wolff-Parkinson-White syndrome.
- Known hypersensitivity to diltiazem or to any of the excipients.
- Known hypersensitivity to itraconazole or to any of the excipients.
- Elevated or abnormal liver enzymes or active liver disease, or who have experienced liver toxicity with other drugs.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Non-randomized, Fixed Sequence Study Assessing the Pharmacokinetics of AZD7986 When Administered Alone and With Multiple Doses of Verapamil and Itraconazole or Diltiazem in Healthy Subjects
This is a phase 1, non-randomized, fixed sequence, 3-period, drug-drug interaction study to assess the pharmacokinetics (PK) of AZD7986 in healthy subjects when administered alone and in combination with multiple doses of verapamil and itraconazole or diltiazem
Read the detailed description
This study will be an open-label, non-randomised, fixed sequence, 3-period study conducted at a single study centre to assess the PK of AZD7986 in healthy subjects when administered alone and in combination with multiple doses of verapamil and itraconazole or diltiazem. An adaptive design with an interim analysis of the PK data from Periods 1 and 2 will be used to determine which of itraconazole or diltiazem will be administered in combination with AZD7986 in Period 3.
Treatments to be administered in a fixed order separated by a washout period:
period 1 - single AZD7986 (25 mg) on Day 1 (1 hour before food), washout 7 days period 2 - verapamil (240 mg extended release formulation) daily 1 hour before food (Day 1 to 10) and a single dose of AZD7986 (25 mg) 1 hour before food (Day 5), washout period 14 days period 3 - subject to interim pharmacokinetic analysis of AZD7986 alone compared with AZD7986 and verapamil combined, either itraconazole (200 mg, oral solution formulation 10mg/mL) administered twice on Day 1 and daily on days 2 to 11 (1 hour before food) plus AZD7986 (25mg) single dose on Day 6 (1 hour before food); or diltiazem (360 mg, extended release formulation) on Days 1 to 13 (1 hour before food) plus AZD7986 (25 mg) 1 hour before food on Day 8.
- Conditions
- Healthy Subjects
- Being tested
- AZD7986, Verapamil, Itraconazole, Diltiazem
- Keywords
- Non-randomized, Verapamil, Itraconazole, Diltiazem, Safety, Tolerability, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD7986Drug
Oral solution, single dose, dilution from concentrate
VerapamilDrug
Extended release tablet for oral use
ItraconazoleDrug
Oral solution
DiltiazemDrug
Extended release capsule
| Study group | Role | What they receive |
|---|---|---|
| AZD7986 (alone) Treatment period 1 | Experimental | AZD7986 (15 mg/mL) 25 mg dosage administered alone Receives: Drug: AZD7986 |
| Verapamil (with AZD7986) Treatment period 2 | Active comparator | Daily administration of verapamil (240 mg, extended release formulation) on Days 1 to 10 plus administration of single dose AZD7986 (25 mg) on Day 5 Receives: Drug: AZD7986; Drug: Verapamil |
| Itraconazole (with AZD7986) Treatment Period 3 | Active comparator | Itraconazole (200 mg, oral solution formulation 10 mg/mL) administered twice on Day 1 and then daily Days 2 to 11 plus single dose AZD7986 (25 mg, tbc) on Day 6 Receives: Drug: AZD7986; Drug: Itraconazole |
| Diltiazem (with AZD7986) Treatment period 3 | Active comparator | Diltiazem (360 mg, extended release formulation) administered Days 1 to 13 plus single dose AZD7986 (25 mg) on Day 8 Receives: Drug: AZD7986; Drug: Diltiazem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of Verapamil and the Effect of Itraconazole on the PK of AZD7986 by Assessment of the Observed Maximum Plasma Concentration (Cmax).
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Measured: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
Effect of Verapamil and the Effect of Itraconazole on the PK of AZD7986 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC).
To assess the effect of verapamil and itraconazole on the PK of AZD7986.
Measured: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
Pharmacokinetics (PK) of AZD7986 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-t]).
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Measured: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
Pharmacokinetics (PK) of AZD7986 by Assessment of Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz).
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Measured: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
Pharmacokinetics (PK) of AZD7986 by Assessment of the Time to Reach Maximum Plasma Concentration (Tmax)
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Measured: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
Pharmacokinetics (PK) of AZD7986 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F).
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Measured: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
Pharmacokinetics (PK) of AZD7986 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F).
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Measured: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC [0 - τ]) of Verapamil, Itraconazole and OH-itraconazole Following Co-administration of AZD7986 With Verapamil or Itraconazole.
To assess the area under the plasma concentration-time curve from time over the dosing interval tau (24 hours) of Verapamil, itraconazole and OH-itraconazole (a metabolite of Itraconazole) following co-administration of AZD7986 with Verapamil or Itraconazole.
Measured: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
Assessment of the Tmax of Verapamil, Itraconazole and OH-itraconazole Following Co-administration of AZD7986 With Verapamil or Itraconazole.
To assess the time to reach maximum observed concentration of Verapamil, Itraconazole and OH-itraconazole (a metabolite of itraconazole) following co-administration of AZD7986 with Verapamil or Itraconazole.
Measured: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2016 (estimated)
- Study start22 Jan 2016
- Primary completion13 Apr 2016
- Study completion13 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy SubjectsStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Annelize Koch, MBChB, FFPM, Principal investigator, Parexel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02653872
- Sponsor's protocol ID
- D6190C00003
- Status last verified
- Jul 2017
- First submitted
- 11 Jan 2016
- Last updated
- 23 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-randomized, Fixed Sequence Study Assessing the Pharmacokinetics of AZD7986 When Administered Alone and With Multiple Doses of Verapamil and Itraconazole or Diltiazem in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02653872
- Acronym / sponsor ID
- D6190C00003
- Conditions
- Healthy Subjects
- Keywords
- Non-randomized, Verapamil, Itraconazole, Diltiazem, Safety, Tolerability, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 22 Jan 2016 (actual)
- Primary completion
- 13 Apr 2016 (actual)
- Study completion
- 13 Apr 2016 (actual)
- First posted
- 12 Jan 2016 (estimated)
- Results
- Posted 23 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1, non-randomized, fixed sequence, 3-period, drug-drug interaction study to assess the pharmacokinetics (PK) of AZD7986 in healthy subjects when administered alone and in combination with multiple doses of verapamil and itraconazole or diltiazem
Detailed description
This study will be an open-label, non-randomised, fixed sequence, 3-period study conducted at a single study centre to assess the PK of AZD7986 in healthy subjects when administered alone and in combination with multiple doses of verapamil and itraconazole or diltiazem. An adaptive design with an interim analysis of the PK data from Periods 1 and 2 will be used to determine which of itraconazole or diltiazem will be administered in combination with AZD7986 in Period 3.
Treatments to be administered in a fixed order separated by a washout period:
period 1 - single AZD7986 (25 mg) on Day 1 (1 hour before food), washout 7 days period 2 - verapamil (240 mg extended release formulation) daily 1 hour before food (Day 1 to 10) and a single dose of AZD7986 (25 mg) 1 hour before food (Day 5), washout period 14 days period 3 - subject to interim pharmacokinetic analysis of AZD7986 alone compared with AZD7986 and verapamil combined, either itraconazole (200 mg, oral solution formulation 10mg/mL) administered twice on Day 1 and daily on days 2 to 11 (1 hour before food) plus AZD7986 (25mg) single dose on Day 6 (1 hour before food); or diltiazem (360 mg, extended release formulation) on Days 1 to 13 (1 hour before food) plus AZD7986 (25 mg) 1 hour before food on Day 8.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AZD7986 (alone) Treatment period 1 | Experimental | Drug: AZD7986AZD7986 (15 mg/mL) 25 mg dosage administered alone |
| Verapamil (with AZD7986) Treatment period 2 | Active comparator | Drug: AZD7986, Drug: VerapamilDaily administration of verapamil (240 mg, extended release formulation) on Days 1 to 10 plus administration of single dose AZD7986 (25 mg) on Day 5 |
| Itraconazole (with AZD7986) Treatment Period 3 | Active comparator | Drug: AZD7986, Drug: ItraconazoleItraconazole (200 mg, oral solution formulation 10 mg/mL) administered twice on Day 1 and then daily Days 2 to 11 plus single dose AZD7986 (25 mg, tbc) on Day 6 |
| Diltiazem (with AZD7986) Treatment period 3 | Active comparator | Drug: AZD7986, Drug: DiltiazemDiltiazem (360 mg, extended release formulation) administered Days 1 to 13 plus single dose AZD7986 (25 mg) on Day 8 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and/or female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venepuncture.
- Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:
- Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post menopausal range(> 40 milli-International unit [mIU]/mL).
- Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation.
Key exclusion criteria (56 listed)
- 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 (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of AZD7986.
- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator.
- Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
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 |
|---|---|---|
| AZD7986Oral solution, single dose, dilution from concentrate | Drug | AZD7986 (alone) Treatment period 1, Diltiazem (with AZD7986) Treatment period 3, Itraconazole (with AZD7986) Treatment Period 3, Verapamil (with AZD7986) Treatment period 2 |
| VerapamilExtended release tablet for oral use | Drug | Verapamil (with AZD7986) Treatment period 2 |
| ItraconazoleOral solution | Drug | Itraconazole (with AZD7986) Treatment Period 3 |
| DiltiazemExtended release capsule | Drug | Diltiazem (with AZD7986) Treatment period 3 |
Primary outcome
Effect of Verapamil and the Effect of Itraconazole on the PK of AZD7986 by Assessment of the Observed Maximum Plasma Concentration (Cmax).
Time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Effect of Verapamil and the Effect of Itraconazole on the PK of AZD7986 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC).
Time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
To assess the effect of verapamil and itraconazole on the PK of AZD7986.
Pharmacokinetics (PK) of AZD7986 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-t]).
Time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Pharmacokinetics (PK) of AZD7986 by Assessment of Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz).
Time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Pharmacokinetics (PK) of AZD7986 by Assessment of the Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Pharmacokinetics (PK) of AZD7986 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F).
Time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Pharmacokinetics (PK) of AZD7986 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F).
Time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
To assess the effect of Verapamil and Itraconazole on the PK of AZD7986.
Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC [0 - τ]) of Verapamil, Itraconazole and OH-itraconazole Following Co-administration of AZD7986 With Verapamil or Itraconazole.
Time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
To assess the area under the plasma concentration-time curve from time over the dosing interval tau (24 hours) of Verapamil, itraconazole and OH-itraconazole (a metabolite of Itraconazole) following co-administration of AZD7986 with Verapamil or Itraconazole.
Assessment of the Tmax of Verapamil, Itraconazole and OH-itraconazole Following Co-administration of AZD7986 With Verapamil or Itraconazole.
Time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose
To assess the time to reach maximum observed concentration of Verapamil, Itraconazole and OH-itraconazole (a metabolite of itraconazole) following co-administration of AZD7986 with Verapamil or Itraconazole.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Annelize Koch, MBChB, FFPM principal investigator
Parexel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD7986, Verapamil and Itraconazole in people with Healthy Subjects, run by AstraZeneca at 1 site 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 56 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 23 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
Yes. Results are posted in the registry (first posted 23 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Effect of Verapamil and the Effect of Itraconazole on the PK of AZD7986 by Assessment of the Observed Maximum Plasma Concentration (Cmax). (time frame: Period 1,2&3: Day1 (AZD7986),Day5 (AZD7986+Verapamil) & Day6 (AZD7986): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12,24,48,72,96,120 & 144 hours post-dose; Period 3: Day6 (Itraconazole): pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,5,8,9,12 & 24 hours post-dose). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Feb 2018; AzTrials last refreshed its copy on 6 Nov 2026.