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CompletedNCT02780713PKUpdated Aug 25, 2021Results posted

A Study to Assess the Pharmacokinetics and Safety of Different Forms and Formulations of AZD9496 in Healthy Subjects

A Phase 1 interventional study of AZD9496 (Reference) and AZD9496 Variant A in Breast Cancer, sponsored by AstraZeneca. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-08-25.

Sponsored by AstraZeneca · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
14
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This is a phase 1 open label single centre study of AZD9496 administered orally in healthy volunteers. The study design involves single administration of different forms, formulations and doses of AZD9496. The study is designed to investigate these different AZD9496 variants. The study will evaluate the pharmacokinetic profiles and the safety and tolerability of the different forms, formulations and doses of AZD9496

This is a fixed sequence study with 5-sequential treatment periods in healthy volunteers. Each volunteer will receive 5 single doses of AZD9496 in different forms, formulations and doses.

Read the detailed description

A phase 1, open-label, single centre study to assess the pharmacokinetics, Safety and tolerability of different forms, formulations and doses of AZD9496 in healthy volunteers. This is a fixed sequence study with 5-sequential treatment periods. Each subject will receive 5 single doses of AZD9496 in different forms, formulations and doses.

  • Treatment period one will assess AZD9496 Variant A: 100mg.
  • Treatment period two will assess AZD9496 Reference form: 100mg.
  • Treatment period 3 will assess one of AZD9496 Variants, B, C or D: 100mg.
  • Treatment period 4 will assess one of AZD9496 Variants, B, C or D: 100mg.
  • Treatment period 5 will assess one of AZD9496 Variants A, B, C or D: *300mg. *Based on a review of pharmacokinetic and safety results from Treatment Periods 1, 3 and 4, a lower dose of 200 mg may be administered in Treatment Period 5.
02

Conditions studied

  • Breast Cancer

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Keywords

  • Breast cancer
  • Healthy volunteers
  • Pharmacokinetics
  • AZD9496
  • Safety
  • Tolerability
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 14 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Provision of signed and dated, written informed consent prior to any study specific procedures.
  2. Healthy male and/or female subjects aged 18 to 65 years with suitable veins for cannulation or repeated venipuncture.
  3. 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 FSH levels in the post-menopausal range (OR) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation
  4. Male subjects aged 18 to 39 years must be vasectomized. Male subjects aged 40 to 65 years must either be vasectomized or have no intention of fathering a child for a period of 6 months after receiving the last dose of IMP.
  5. Have a body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive.
  6. Values for AST, ALT, TBL, GGT and ALP must be at or below the upper limit of normal ranges at screening.

Exclusion criteria

Exclusion Criteria:

  1. 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.
  2. 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.
  3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
  4. Previous history of venous or arterial thromboembolism or thrombophilia.
  5. History of endometrial polyps, endometrial cancer, atypical endometrial hyperplasia, or other endometrial disorders unless subjects have undergone total hysterectomy and there is no evidence of active disease (females only).
  6. Any clinically significant abnormalities in clinical chemistry (other than Inclusion no.6), hematology, or urinalysis results at screening, as judged by the investigator.
  7. Any clinically significant abnormal findings in supine vital signs, after 10 minutes of supine rest, at screening and/or admission to the unit, defined as: (a) Systolic blood pressure \< 90 mmHg or ≥ 150 mmHg (b) Diastolic blood pressure \< 50 mmHg or ≥ 95 mmHg and (c) Heart rate \< 45 or > 90 beats per minute
  8. Any clinically important abnormalities in rhythm, conduction or morphology of the resting 12-lead ECG that, as judged by the investigator, that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or pronounced left ventricular hypertrophy.
  9. Prolonged QTcF > 460 ms for females and QTcF > 450 ms for males or family history of long QT syndrome.
  10. PR (PQ) interval shortening \< 110 ms or evidence of ventricular pre-excitation).
  11. PR (PQ) interval prolongation > 240 ms, intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block.
  12. Persistent or intermittent complete bundle branch block with QRS > 120 ms or evidence of pronounced ventricular hypertrophy or pre-excitation.
  13. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody.
  14. Known or suspected history of drug abuse, as judged by the investigator.
  15. Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening.
  16. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol, as judged by the investigator.
  17. Positive screen for drugs of abuse, alcohol or cotinine at screening or on each admission to the unit.
  18. 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 AZD9496.
  19. Excessive intake of caffeine/xanthine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the investigator.
  20. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
  21. Use of any 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 Note: Hormonal replacement therapy is not allowed for females.
  22. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening
  23. 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. The period of exclusion is 3 months after the final dose from previous study or 1 month after the last visit of previous study, whichever is the longest. ote: Subjects consented and screened, but not dosed in this study or a previous phase I study, are not excluded.
  24. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives
  25. 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.
  26. Subjects who are vegans or have medical dietary restrictions.
  27. Subjects who cannot communicate reliably with the investigator.
  28. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
14 participants (actual)

Study arms

  • Experimental
    AZD9496

    This is a fixed sequence study with 5-sequential treatment periods in healthy volunteers. Each volunteer will receive 5 single doses of AZD9496 in different forms, formulations and doses. 1. Treatment period 1 will assess AZD9496 Variant A: 100mg. 2. Treatment period 2 will assess AZD9496 Reference: 100mg. 3. Treatment period 3 will assess one of AZD9496 Variants, B, C or D: 100mg. 4. Treatment period 4 will assess one of AZD9496 Variants, B, C or D: 100mg. 5. Treatment period 5 will assess one of AZD9496 Variants A, B, C or D: \*300mg. \*Based on a review of PK and safety results from Treatment Periods 1, 3 and 4, a lower dose of 200 mg may be administered in Treatment Period 5

    Drug: AZD9496 (Reference) · Drug: AZD9496 Variant A · Drug: AZD9496 Variant B · Drug: AZD9496 Variant C · Drug: AZD9496 Variant D

Interventions

  • DrugAZD9496 (Reference)

    AZD9496 (Reference)

  • DrugAZD9496 Variant A

    AZD9496 Variant A.

  • DrugAZD9496 Variant B

    AZD9496 Variant B

  • DrugAZD9496 Variant C

    AZD9496 Variant C

  • DrugAZD9496 Variant D

    AZD9496 Variant D

06

What researchers measure

Primary outcomes

  1. Pharmacokinetics: Maximum Plasma Concentration (Cmax) for AZD9496 and Its Metabolites at Each Treatment Period.

    To evaluate maximum observed plasma concentration (Cmax) for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.

    Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  2. Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for AZD9496 and Its Metabolites at Each Treatment Period

    To evaluate the area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUC (0-t) of AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation

    Time frame: Regular Pharmacokinetic measurement: At Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  3. Pharmacokinetics: Maximum Plasma Concentration (Cmax) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference

    To evaluate maximum plasma concentration (Cmax) of capsule variants by comparing with reference AZD9496

    Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  4. Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference

    To evaluate area under curve from time zero to time with last observation (AUC0-t) of variants by comparing with reference AZD9496

    Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  5. Pharmacokinetics: Area Under the Curve From Time Zero to Infinity for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference

    To evaluate area under the curve from time zero to time infinity (AUC 0-infinity) of variants by comparing with reference AZD9496

    Time frame: Regular Pharmacokinnetic measurement Pre-dose, 0.5, 1, 1.5, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24, and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  6. Pharmacokinetics: Area Under the Curve From Time Zero to Infinity (AUC 0-infinity) for AZD9496 and Metabolites at Each Treatment Period

    To evaluate area under the curve from time zero to infinity (AUC 0-infinity) for AZD9496 and its metabolites

    Time frame: Regular pharmacokinetic measurement pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

Secondary outcomes

  1. Time to Reach Maximum Observed Plasma Concentration (Tmax) for AZD9496 and Its Metabolites at Each Treatment Period.

    To evaluate time to reach maximum observed plasma concentration (Tmax) for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  2. Effective Half-life ( t½,Eff) for AZD9496 and Its Metabolites at Each Treatment Period

    To evaluate effective half-life (t½,eff), for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.

    Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  3. Metabolite to Parent Ratios (MRAUC0-t, MRCmax, MRAUC) at Each Treatment Period.

    To evaluate metabolite to parent ratios (MRAUC0-t, MRCmax, MRAUC) at each treatment period.

    Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  4. Pharmacokinetics: AUC From Time Zero to 12 and 24 Hours Post-dose for AZD9496 and Its Metabolites at Each Treatment Period

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  5. Pharmacokinetics: The Terminal Elimination Half-life (t½,λz) for AZD9496 and Its Metabolites at Each Treatment Period

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

  6. Pharmacokinetics: Apparent Volume of Distribution (Vss/F) of AZD9496 and Its Metabolites at Each Treatment Period

    Time frame: Day 1, Day 2, Day 3 and Day 4

  7. Pharmacokinetics: Apparent Oral Clearance (CL/F) of AZD9496 and Its Metabolites at Each Treatment Period

    Time frame: Day 1, Day 2, Day 3 and Day 4

  8. Pharmacokinetics: Apparent Terminal Elimination Rate Constant (λz) of AZD9496 and Its Metabolites at Each Treatment Period

    Time frame: Day 1, Day 2, Day 3, Day 4

  9. Pharmacokinetics: Mean Residence Time (MRT) of AZD9496 and Its Metabolites at Each Treatment Period

    Time frame: Day 1, Day 2, Day 3, Day 4

07

Results

Posted Aug 25, 2021
Limitations and caveats
Data from all analysed secondary pharmacokinetic parameters are presented.

Participant flow

At the United States (US, 1 site), 14 healthy participants were treated with AZD9496 (1 dose at fasted state) in 5 treatment periods: Formulation Variants A, B \& C (doses 1,3, \& 4), reference (dose 2) and formulation Variant B (dose 5). Each subject was involved in the study for approximately 10 to 12 weeks.

Period 1: Variant A (100mg)
Participant flow — Period 1: Variant A (100mg)
MilestoneTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
Started140000
Completed140000
Not completed00000
Period 2: Reference (100mg)
Participant flow — Period 2: Reference (100mg)
MilestoneTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
Started014000
Completed014000
Not completed00000
Period 3: Variant B (100mg)
Participant flow — Period 3: Variant B (100mg)
MilestoneTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
Started001400
Completed001200
Not completed00200
Withdrew: Withdrawal by subject00200
Period 4: Variant C (100mg)
Participant flow — Period 4: Variant C (100mg)
MilestoneTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
Started000120
Completed000120
Not completed00000
Period 5: Variant B (300mg)
Participant flow — Period 5: Variant B (300mg)
MilestoneTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
Started000012
Completed000012
Not completed00000

Outcome measures

PrimaryPharmacokinetics: Maximum Plasma Concentration (Cmax) for AZD9496 and Its Metabolites at Each Treatment Period.

To evaluate maximum observed plasma concentration (Cmax) for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.

Time frame:
Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Geometric mean · ng/mL
Pharmacokinetics: Maximum Plasma Concentration (Cmax) for AZD9496 and Its Metabolites at Each Treatment Period.
ng/mLTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD949664.85 ± 73.54381.0 ± 55.83138.2 ± 75.3591.83 ± 52.13550.9 ± 41.85
M310.30 ± 98.9362.98 ± 76.9123.56 ± 74.3014.47 ± 39.0198.72 ± 54.80
M51.102 ± 85.277.409 ± 75.182.454 ± 80.351.520 ± 42.6711.71 ± 49.60
PrimaryPharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for AZD9496 and Its Metabolites at Each Treatment Period

To evaluate the area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUC (0-t) of AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation

Time frame:
Regular Pharmacokinetic measurement: At Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Geometric mean · ng*h/mL
Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for AZD9496 and Its Metabolites at Each Treatment Period
ng*h/mLTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD9496383.4 ± 60.541207 ± 53.01677.8 ± 50.08523.0 ± 26.772322 ± 32.12
M346.71 ± 124.65196.6 ± 80.92111.7 ± 62.0078.23 ± 65.96411.3 ± 57.56
M54.872 ± 98.9123.11 ± 73.6811.05 ± 62.207.614 ± 57.9346.42 ± 49.23
PrimaryPharmacokinetics: Maximum Plasma Concentration (Cmax) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference

To evaluate maximum plasma concentration (Cmax) of capsule variants by comparing with reference AZD9496

Time frame:
Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Geometric mean · Ratio
Pharmacokinetics: Maximum Plasma Concentration (Cmax) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
RatioDN Ratio - Variant A (100 mg): Ref (100 mg)DN Ratio - Variant B (100 mg) : Ref (100 mg)DN Ratio - Variant C (100 mg) : Ref (100 mg)
Pharmacokinetics: Maximum Plasma Concentration (Cmax) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference0.1702 ± 90.940.3440 ± 110.400.2285 ± 89.40
Statistical analysis
  • DN Ratio - Variant A (100 mg): Ref (100 mg) · Percentage: 17.02 · 95% CI 11.79 to 24.58
  • DN Ratio - Variant B (100 mg) : Ref (100 mg) · Percentage: 36.28 · 95% CI 23.84 to 55.20
  • DN Ratio - Variant C (100 mg) : Ref (100 mg) · Percentage: 24.10 · 95% CI 16.84 to 34.48
PrimaryPharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference

To evaluate area under curve from time zero to time with last observation (AUC0-t) of variants by comparing with reference AZD9496

Time frame:
Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Geometric mean · Ratio
Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
RatioDN Ratio - Variant A (100 mg): Ref (100 mg)DN Ratio - Variant B (100 mg) : Ref (100 mg)AZD9496 - Variant C (100 mg)
Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference0.3175 ± 46.350.5227 ± 50.950.4033 ± 33.15
Statistical analysis
  • DN Ratio - Variant A (100 mg): Ref (100 mg) · Percentage: 31.75 · 95% CI 25.77 to 39.12
  • DN Ratio - Variant B (100 mg) : Ref (100 mg) · Percentage: 54.17 · 95% CI 42.16 to 69.60
  • AZD9496 - Variant C (100 mg) · Pecentage: 41.23 · 95% CI 34.79 to 48.86
SecondaryTime to Reach Maximum Observed Plasma Concentration (Tmax) for AZD9496 and Its Metabolites at Each Treatment Period.

To evaluate time to reach maximum observed plasma concentration (Tmax) for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Median · Hours
Time to Reach Maximum Observed Plasma Concentration (Tmax) for AZD9496 and Its Metabolites at Each Treatment Period.
HoursTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD94964.25 (1.50 to 5.60)2.25 (1.50 to 3.48)3.52 (2.50 to 5.03)4.25 (2.50 to 5.02)4.25 (2.50 to 6.05)
M34.50 (2.00 to 5.60)2.50 (1.50 to 4.67)3.77 (2.98 to 6.02)5.00 (3.00 to 5.12)4.26 (2.50 to 6.05)
M54.50 (2.00 to 5.60)2.50 (1.50 to 4.05)4.00 (2.50 to 5.50)4.99 (3.00 to 5.12)4.51 (2.50 to 6.05)
SecondaryEffective Half-life ( t½,Eff) for AZD9496 and Its Metabolites at Each Treatment Period

To evaluate effective half-life (t½,eff), for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.

Time frame:
Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Mean · Hours
Effective Half-life ( t½,Eff) for AZD9496 and Its Metabolites at Each Treatment Period
HoursTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD94961.34 ± 0.451.11 ± 0.151.51 ± 0.681.56 ± 0.361.36 ± 0.31
M31.16 ± 0.361.09 ± 0.172.02 ± 1.841.57 ± 0.471.28 ± 0.28
M51.15 ± 0.271.06 ± 0.151.54 ± 0.701.42 ± 0.361.23 ± 0.26
SecondaryMetabolite to Parent Ratios (MRAUC0-t, MRCmax, MRAUC) at Each Treatment Period.

To evaluate metabolite to parent ratios (MRAUC0-t, MRCmax, MRAUC) at each treatment period.

Time frame:
Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Geometric mean · Ratio
Metabolite to Parent Ratios (MRAUC0-t, MRCmax, MRAUC) at Each Treatment Period.
RatioTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
M3 - MRAUC(0-t)0.122 ± 48.120.163 ± 30.750.165 ± 33.490.150 ± 41.380.177 ± 30.28
M5 - MRAUC(0-t)0.013 ± 33.810.019 ± 22.070.016 ± 23.060.015 ± 32.710.020 ± 21.32
M3 - MRCmax0.159 ± 37.680.165 ± 25.970.170 ± 30.680.158 ± 36.290.179 ± 27.25
M5 - MRCmax0.017 ± 30.160.019 ± 21.010.018 ± 31.230.017 ± 33.790.022 ± 20.22
M3 - MRAUC—0.173 ± 21.110.172 ± 7.81—0.193 ± 39.07
M5 - MRAUC—0.020 ± 14.910.018 ± 10.90—0.021 ± 26.57
PrimaryPharmacokinetics: Area Under the Curve From Time Zero to Infinity for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference

To evaluate area under the curve from time zero to time infinity (AUC 0-infinity) of variants by comparing with reference AZD9496

Time frame:
Regular Pharmacokinnetic measurement Pre-dose, 0.5, 1, 1.5, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24, and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Geometric mean · Ratio
Pharmacokinetics: Area Under the Curve From Time Zero to Infinity for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
RatioTreatment Period 1Treatment Period 3Treatment Period 4
Pharmacokinetics: Area Under the Curve From Time Zero to Infinity for Variant A, B and C of AZD9496 Compared to the AZD9496 ReferenceNA ± NA0.6186 ± 37.260.4055 ± 48.13
PrimaryPharmacokinetics: Area Under the Curve From Time Zero to Infinity (AUC 0-infinity) for AZD9496 and Metabolites at Each Treatment Period

To evaluate area under the curve from time zero to infinity (AUC 0-infinity) for AZD9496 and its metabolites

Time frame:
Regular pharmacokinetic measurement pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Geometric mean · ng*h/mL
Pharmacokinetics: Area Under the Curve From Time Zero to Infinity (AUC 0-infinity) for AZD9496 and Metabolites at Each Treatment Period
ng*h/mLTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD9496NA ± NA1238 ± 46.88968.1 ± 30.12604.7 ± 18.372790 ± 22.97
M3—253.2 ± 58.9799.9 ± 64.1056.9 ± 30.78420.6 ± 76.41
M55.93 ± 95.5324.09 ± 76.0011.15 ± 65.47—54.84 ± 47.54
SecondaryPharmacokinetics: AUC From Time Zero to 12 and 24 Hours Post-dose for AZD9496 and Its Metabolites at Each Treatment Period
Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Geometric mean · ng*h/mL
Pharmacokinetics: AUC From Time Zero to 12 and 24 Hours Post-dose for AZD9496 and Its Metabolites at Each Treatment Period
ng*h/mLTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD9496 AUC 0-12 Hours256.2 ± 65.671194 ± 51.83515.3 ± 57.4326.3 ± 36.181920 ± 38.5
AZD9496 AUC 0-24 Hours299.9 ± 60.131306 ± 44.9614.8 ± 49.08411.7 ± 282130 ± 36.83
M3 AUC 0-12 Hours63.02 ± 72.17377.3 ± 23.8691.52 ± 57.3262.41 ± 33.9391.6 ± 46.7
M3 AUC 0-24 Hours73.26 ± 71.57NA ± NA114.9 ± 47.4391.49 ± 32.74490.4 ± 47.82
M5 AUC 0-12 Hours6.162 ± 78.9537.83 ± 33.768.646 ± 74.315.953 ± 31.7840.2 ± 49.71
M5 AUC 0-24 Hours7.417 ± 65.09NA ± NA10.09 ± 60.58.32 ± 27.7646.57 ± 49.04
SecondaryPharmacokinetics: The Terminal Elimination Half-life (t½,λz) for AZD9496 and Its Metabolites at Each Treatment Period
Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Reported as:
Mean · Hours
Pharmacokinetics: The Terminal Elimination Half-life (t½,λz) for AZD9496 and Its Metabolites at Each Treatment Period
HoursTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD9496NA ± NA2.59 ± 1.758.95 ± 7.5515.66 ± 4.479.65 ± 3.96
M3NA ± NA1.34 ± 0.392.19 ± 2.131.89 ± 0.573.69 ± 2.70
M51.18 ± 0.471.89 ± 1.351.41 ± 0.55—5.06 ± 2.25
SecondaryPharmacokinetics: Apparent Volume of Distribution (Vss/F) of AZD9496 and Its Metabolites at Each Treatment Period
Time frame:
Day 1, Day 2, Day 3 and Day 4
Reported as:
Mean · L
Pharmacokinetics: Apparent Volume of Distribution (Vss/F) of AZD9496 and Its Metabolites at Each Treatment Period
LTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD9496—277.5 ± 127.31291 ± 10973495 ± 1532920.7 ± 392.1
SecondaryPharmacokinetics: Apparent Oral Clearance (CL/F) of AZD9496 and Its Metabolites at Each Treatment Period
Time frame:
Day 1, Day 2, Day 3 and Day 4
Reported as:
Mean · L/h
Pharmacokinetics: Apparent Oral Clearance (CL/F) of AZD9496 and Its Metabolites at Each Treatment Period
L/hTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD9496NA ± NA80.8 ± 39.8107.0 ± 32.7167.5 ± 30.1110.0 ± 26.7
SecondaryPharmacokinetics: Apparent Terminal Elimination Rate Constant (λz) of AZD9496 and Its Metabolites at Each Treatment Period
Time frame:
Day 1, Day 2, Day 3, Day 4
Reported as:
Geometric mean · T-1
Pharmacokinetics: Apparent Terminal Elimination Rate Constant (λz) of AZD9496 and Its Metabolites at Each Treatment Period
T-1Treatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD9496NA ± NA0.3132 ± 58.960.1236 ± 183.170.0459 ± 31.050.0777 ± 46.67
M3NA ± NA0.537 ± 29.690.422 ± 88.140.380 ± 34.170.230 ± 75.62
M50.618 ± 38.360.426 ± 55.480.526 ± 41.77—0.154 ± 65.20
SecondaryPharmacokinetics: Mean Residence Time (MRT) of AZD9496 and Its Metabolites at Each Treatment Period
Time frame:
Day 1, Day 2, Day 3, Day 4
Reported as:
Geometric mean · Hours
Pharmacokinetics: Mean Residence Time (MRT) of AZD9496 and Its Metabolites at Each Treatment Period
HoursTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5
AZD9496NA ± NA3.122 ± 23.778.992 ± 107.7619.73 ± 52.637.939 ± 29.73

Adverse events

Collected over From enrollment until the final follow-up visit (5 to 7 days after last dose). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment Period 10/14 (0%)0/14 (0%)2/14 (14.3%)
Treatment Period 20/14 (0%)0/14 (0%)1/14 (7.1%)
Treatment Period 30/12 (0%)0/12 (0%)1/12 (8.3%)
Treatment Period 40/12 (0%)0/12 (0%)0/12 (0%)
Treatment Period 50/12 (0%)0/12 (0%)1/12 (8.3%)
All Participants0/14 (0%)0/14 (0%)5/14 (35.7%)
Most frequent other events
Most frequent other events
EventTreatment Period 1Treatment Period 2Treatment Period 3Treatment Period 4Treatment Period 5All Participants
Musculoskeletal painMusculoskeletal and connective tissue disorders0/140/141/120/120/121/14
Body tineaInfections and infestations0/140/140/120/121/121/14
Back painMusculoskeletal and connective tissue disorders1/140/140/120/120/121/14
RhinorrheaRespiratory, thoracic and mediastinal disorders1/140/140/120/120/121/14
ErythemaSkin and subcutaneous tissue disorders0/141/140/120/120/121/14

Baseline characteristics

Age, Continuous
Age, Continuous(Years)All Participants
Mean49.6 ± 6.22
Sex/Gender, Customized
Sex/Gender, Customized(Participants)All Participants
Male14
Female0
08

Study locations

1 site
  • Research Site
    Baltimore, Maryland 21225, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 25, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02780713
Lead sponsor
AstraZeneca
Collaborators
Parexel
Responsible party
Sponsor
First posted
May 23, 2016
Start date
Jun 2, 2016
Primary completion
Sep 20, 2016
Completion
Sep 20, 2016
Results posted
Aug 25, 2021
Last update
Aug 25, 2021

Study contacts

Dr. Ronald Goldwater
principal investigator · Parexel

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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