Healthy VolunteersPhase 1Rel BioNCT03710434
AZD4635 Relative Bioavailability Study
A Phase 1 study testing AZD4635 50 mg nano-suspension (reference), AZD4635 solid oral formulation - fasted and AZD4635 solid oral formulation - fed in people with Healthy Volunteers, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
To investigate the pharmacokinetics and relative bioavailability of AZD4635 solid oral formulation and compare with the nano-suspension reference formulation with the option to assess food effect, pH effect and absolute bioavailability Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- AZD4635 50 mg nano-suspension (reference), AZD4635 solid oral formulation - fasted and AZD4635 solid oral formulation - fed
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Nov 2018to 2 Apr 2019
- 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 55 years
- Men only
- 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 subjects aged 18 to 55 years with suitable veins for cannulation or repeated venepuncture and IV infusion.
- Have a body mass index of 18.0 to 32.0 kg/m2, and weigh at least 50 kg and no more than 100 kg.
- Must be willing and able to communicate and participate in the whole study
- Must agree to adhere to the contraception requirements, as precaution should avoid fathering a child by either true abstinence or use together, with their female partner/spouse, a highly effective contraception form of birth control in combination with a barrier method, starting from the time of AZD4635 administration until 90 days after the last dose of AZD4635.
Who cannot join
- History of any clinically significant disease or disorder which in investigator opinion, may put volunteer at risk because of participation in the study, or influence results of volunteer'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.
- Presence of refractory nausea and vomiting or chronic gastrointestinal diseases.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- Any confirmed clinically significant abnormalities in clinical chemistry, haematology or urinalysis as judged by the investigator
- Any confirmed clinically significant abnormal findings in vital signs, as judged by investigator.
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- BP >140/90 mmHg or history of hypertension.
- Any confirmed clinically significant abnormal findings in 12-lead ECG, as judged by investigator.
- Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
- Known or suspected history of drug or alcohol abuse within the past 2 years, as judged by the investigator.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit, whichever is longest. Note: subjects consented and screened, but not randomized in this study or a previous Phase I study are not excluded.
- Plasma donation within 1 month of screening or any blood donation/loss of more than 500 mL of blood during the 3 months prior to screening.
- 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 AZD4635 or the formulation excipients. Hayfever is allowed unless it is active.
- Current smokers and those who have smoked within last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission.
- Current users of e-cigarettes and nicotine replacement products and those who have used these products within last 12 months.
- Positive screen for drugs of abuse at screening or admission to the clinical unit or positive screen for alcohol at screening or admission to the clinical unit.
- Herbal preparations/medications are not allowed throughout the study. These herbal medications include, but are not limited to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng. Subjects should stop using these herbal medications 14 days prior to the first dose of AZD4635.
- Use of any prescribed or nonprescribed medication including antacids, H2 antagonists, PPI, analgesics (other than paracetamol/acetaminophen up to 4 g/day), vitamins and minerals during the two weeks prior to first administration of IMP or longer if medication has a longer half-life. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor.
- Known or suspected history of alcohol or drug abuse or regular alcohol consumption in males >21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
- Subjects who are study site employees, or immediate family members of a study site or sponsor employee
- Subjects who have previously been enrolled in this study or have previously received AZD4635.
- Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study
- Subjects who have been enrolled in an ADME study in the last 12 months.
- Subjects with Gilberts Syndrome or a history of cholecystectomy or gall stones.
- Judgment by investigator that volunteer should not participate in study if they have any ongoing or recent (ie, during the screening period) minor medical complaints that may interfere with the interpretation of the study data or are considered unlikely to comply with the study procedures, restrictions and requirements.
- Failure to satisfy the investigator of fitness to participate for any other reason.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open-Label Study to Assess the Pharmacokinetics and Relative Bioavailability of AZD4635 in Non-Smoking Healthy Male Subjects, With the Option to Assess Food Effect, pH Effect and Absolute Bioavailability
To investigate the pharmacokinetics and relative bioavailability of AZD4635 solid oral formulation and compare with the nano-suspension reference formulation with the option to assess food effect, pH effect and absolute bioavailability
Read the detailed description
This is a single centre, phase 1, open-label randomised, 2-part study to assess the pharmacokinetics and relative bioavailability of AZD4635 in non-smoking healthy male subjects, with the option to assess food effect, pH effect and absolute bioavailability. It is planned to enrol 20 subjects who will participate in both parts of the study. Subjects will receive a single-dose of AZD4635 in 6 dosing periods with a minimum washout of 9 days between doses.
Part A is a 2-period randomised crossover study of single doses of AZD4635. Subjects will be randomised to receive 50mg AZD4635 nano-suspension (reference) or 50mg AZD4635 solid oral formulation, in the fasted state.
Part B is a 4-period, open-label, randomised, crossover study of single doses of AZD4635 in the same subjects from Part A. The treatments selected for Part B will depend on the outcome of interim analyses of AZD4635 exposure. Subjects will receive 2 of the following 4 treatments in dosing periods 3 and 4:
- A single dose of AZD4635 solid oral formulation dose after a high fat meal
- A single dose of AZD4635 solid oral formulation co-administered with a proton pump inhibitor (PPI), lansoprazole (fasted state)
- A different single dose (XX mg) of AZD4635 solid oral formulation (fasted state)
- Another different single dose (YY mg) of AZD4635 solid oral formulation (fasted state)
Periods 5 and 6 is a 2-period randomised crossover of two variants of AZD4635 solid oral formulation. Subjects will be randomised to receive AZD4635 solid oral formulation variant 1 in the fasted state or AZD4635 solid oral formulation variant 2 in the fasted state. In Periods 5 and 6, Part B an IV microtracer dose of [14C] AZD4635 with solid oral formulation, variant 1 will be administered.
- Conditions
- Healthy Volunteers
- Being tested
- AZD4635 50 mg nano-suspension (reference), AZD4635 solid oral formulation - fasted, AZD4635 solid oral formulation - fed, Lansoprazole and AZD4635 50 mg solid oral formulation, AZD4635 solid oral formulation variant 1 - fasted
- Keywords
- Phase 1, healthy, bioavailability, pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4635 50 mg nano-suspension (reference)Drug
Subjects will receive a single dose of AZD4635 50 mg nano-suspension (reference) in the fasted state.
AZD4635 solid oral formulation - fastedDrug
Subjects will receive a single dose of AZD4635 solid oral formulation, in the fasted state.
AZD4635 solid oral formulation - fedDrug
Subjects will receive a single dose of AZD4635 solid oral formulation, in the fed state.
Lansoprazole and AZD4635 50 mg solid oral formulationDrug
Subjects will receive lansoprazole 30 mg BID for 5 days followed by a single dose of AZD4635 50 mg solid oral formulation in the fasted state.
AZD4635 solid oral formulation variant 1 - fastedDrug
Subjects will receive a single dose of AZD4635 solid oral formulation, variant 1 in the fasted state.
AZD4635 solid oral formulation variant 2 - fastedDrug
Subjects will receive a single dose of AZD4635 solid oral formulation, variant 2 in the fasted state.
[14C] AZD4635 IV microtracer - fastedDrug
Subjects will receive a single dose of [14C] AZD4635 IV microtracer. This intervention will be co-administered with AZD4635 solid oral formulation variant 1.
| Study group | Role | What they receive |
|---|---|---|
| Part A - nano-suspension | Experimental | Subjects will receive single dose of AZD4635 50mg nano-suspension (reference) in the fasted state. Receives: Drug: AZD4635 50 mg nano-suspension (reference) |
| Part A - solid oral formulation | Experimental | Subjects will receive single dose of AZD4635 50mg solid oral formulation, in the fasted state. Receives: Drug: AZD4635 solid oral formulation - fasted |
| Part B-solid oral formulation with food | Experimental | Subjects will receive a single dose AZD4635 solid oral formulation after high fat meal. Receives: Drug: AZD4635 solid oral formulation - fed |
| Part B - solid oral formulation with PPI | Experimental | Subjects will receive 30 mg lansoprazole BID and a single dose of AZD4635 solid oral formulation in the fasted state. Receives: Drug: Lansoprazole and AZD4635 50 mg solid oral formulation |
| Part B - dose exploration 1 | Experimental | If dose adjustment is required, subjects will receive a different single dose (XX mg) of AZD4635 solid oral formulation, in the fasted state. Receives: Drug: AZD4635 solid oral formulation - fasted |
| Part B - dose exploration 2 | Experimental | If dose adjustment is required, subjects will receive a different single dose (YY mg) of AZD4635 solid oral formulation, in the fasted state. Receives: Drug: AZD4635 solid oral formulation - fasted |
| Part B - variant 1 | Experimental | Subjects will receive a single dose of AZD4635 solid oral formulation, variant 1 in the fasted state and optional [14C] AZD4635 IV microtracer. Receives: Drug: AZD4635 solid oral formulation variant 1 - fasted; Drug: [14C] AZD4635 IV microtracer - fasted |
| Part B - variant 2 | Experimental | Subjects will receive a single dose of AZD4635 solid oral formulation, variant 2 in the fasted state. Receives: Drug: AZD4635 solid oral formulation variant 2 - fasted |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax) of AZD4635 solid oral formulation and nano-suspension (reference)
Assessment of maximum concentration (Cmax) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Exposure to AZD4635 solid oral formulation and nano-suspension (reference)
Assessment of exposure through measurement of area under the curve (AUC) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Secondary outcomes (17)
Time to maximum concentration (tmax) of AZD4635 solid oral formulation variants 1 and 2 in plasma
Assessment of time to maximum concentration (tmax) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Maximum concentration (Cmax) of AZD4635 solid oral formulation variants 1 and 2 in plasma
Assessment of maximum concentration (Cmax) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to time of last measurable concentration (AUClast) for AZD4635 solid oral formulation variants 1 and 2
Assessment of exposure through measurement of area under the curve (AUClast) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to 48 hours (AUC 0-48) for AZD4635 solid oral formulation variants 1 and 2
Assessment of exposure through measurement of area under the curve (AUC 0-48) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Area under the plasma concentration-time curve from zero to infinity (AUC 0-inf.) for AZD4635 solid oral formulation variants 1 and 2
Exposure to AZD4635 through measurement of area under the curve (AUC 0-inf.) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Determine absolute bioavailability (F) of AZD4635
Absolute bioavailability (F) will be calculated from area under the plasma concentration versus time curve (AUC) of the oral dose of AZD4635/ AUC of the IV dose of [14C]AZD4635 x IV dose/oral dose /100
Measured: Predose, 0.25h, 0.33h, 0.42h, 0.5h, 0.58h, 0.67h, 0.75h, 1h, 1.25h, 1.5h, 2h, 2.5h, 4.5h, 6.5h, 8.5h, 12.5h, 24h 48h, 72h, 96h, 120h
Time to maximum concentration (tmax) of AZD4635 solid oral formulation in plasma in fasted and fed state (optional)
Assessment of time to maximum concentration (tmax) in plasma in fasted and fed state
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Maximum concentration (Cmax) of AZD4635 solid oral formulation in plasma in fasted and fed state (optional)
Assessment of maximum concentration (Cmax) in plasma in fasted and fed state
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to time of last measurable concentration (AUClast) for AZD4635 solid oral formulation in fasted and fed state (optional)
Assessment of exposure in fasted and fed state through measurement of area under the curve (AUClast) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to 48 hours (AUC 0-48) for AZD4635 solid oral formulation in fasted and fed state (optional)
Assessment of exposure in fasted and fed state through measurement of area under the curve (AUC 0-48) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Area under the plasma concentration-time curve from zero to infinity (AUC 0-inf.) for AZD4635 solid oral formulation in fasted and fed state (optional)
Assessment of exposure in fasted and fed state through measurement of area under the curve (AUC 0-inf.) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Time to maximum concentration (tmax) of AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Assessment of time to maximum concentration (tmax) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Maximum concentration (Cmax) of AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Assessment of maximum concentration (Cmax) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to time of last measurable concentration (AUClast) for AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Assessment of exposure through measurement of area under the curve (AUClast) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to 48 hours (AUC 0-48) for AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Assessment of exposure through measurement of area under the curve (AUC 0-48) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Area under the plasma concentration-time curve from zero to infinity (AUC 0-inf.) for AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Assessment of exposure through measurement of area under the curve (AUC 0-inf.) in plasma
Measured: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Number of adverse events (AE) experienced by subjects
Safety and tolerability assessed through incidence of AE
Measured: Approximately 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2018
- Study start1 Nov 2018
- Primary completion2 Apr 2019
- Study completion2 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quotient Sciences
- Responsible party
- Sponsor
- Investigators
- Sharan Sidhu, MBChB, BAO, MRCS, MFPM, Principal investigator, Quotient Sciences Limited (indemnified by Medical Protection Society)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03710434
- Sponsor's protocol ID
- D8730C00002
- Other IDs
- 2018-003366-14, 2018
- Acronym
- Rel Bio
- Status last verified
- May 2020
- First submitted
- 16 Oct 2018
- Last updated
- 7 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label Study to Assess the Pharmacokinetics and Relative Bioavailability of AZD4635 in Non-Smoking Healthy Male Subjects, With the Option to Assess Food Effect, pH Effect and Absolute Bioavailability
- ClinicalTrials.gov ID
- NCT03710434
- Acronym / sponsor ID
- Rel Bio / D8730C00002
- Conditions
- Healthy Volunteers
- Keywords
- Phase 1, healthy, bioavailability, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Quotient Sciences
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 2 Apr 2019 (actual)
- Study completion
- 2 Apr 2019 (actual)
- First posted
- 18 Oct 2018 (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.
To investigate the pharmacokinetics and relative bioavailability of AZD4635 solid oral formulation and compare with the nano-suspension reference formulation with the option to assess food effect, pH effect and absolute bioavailability
Detailed description
This is a single centre, phase 1, open-label randomised, 2-part study to assess the pharmacokinetics and relative bioavailability of AZD4635 in non-smoking healthy male subjects, with the option to assess food effect, pH effect and absolute bioavailability. It is planned to enrol 20 subjects who will participate in both parts of the study. Subjects will receive a single-dose of AZD4635 in 6 dosing periods with a minimum washout of 9 days between doses.
Part A is a 2-period randomised crossover study of single doses of AZD4635. Subjects will be randomised to receive 50mg AZD4635 nano-suspension (reference) or 50mg AZD4635 solid oral formulation, in the fasted state.
Part B is a 4-period, open-label, randomised, crossover study of single doses of AZD4635 in the same subjects from Part A. The treatments selected for Part B will depend on the outcome of interim analyses of AZD4635 exposure. Subjects will receive 2 of the following 4 treatments in dosing periods 3 and 4:
- A single dose of AZD4635 solid oral formulation dose after a high fat meal
- A single dose of AZD4635 solid oral formulation co-administered with a proton pump inhibitor (PPI), lansoprazole (fasted state)
- A different single dose (XX mg) of AZD4635 solid oral formulation (fasted state)
- Another different single dose (YY mg) of AZD4635 solid oral formulation (fasted state)
Periods 5 and 6 is a 2-period randomised crossover of two variants of AZD4635 solid oral formulation. Subjects will be randomised to receive AZD4635 solid oral formulation variant 1 in the fasted state or AZD4635 solid oral formulation variant 2 in the fasted state. In Periods 5 and 6, Part B an IV microtracer dose of [14C] AZD4635 with solid oral formulation, variant 1 will be administered.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part A - nano-suspension | Experimental | Drug: AZD4635 50 mg nano-suspension (reference)Subjects will receive single dose of AZD4635 50mg nano-suspension (reference) in the fasted state. |
| Part A - solid oral formulation | Experimental | Drug: AZD4635 solid oral formulation - fastedSubjects will receive single dose of AZD4635 50mg solid oral formulation, in the fasted state. |
| Part B-solid oral formulation with food | Experimental | Drug: AZD4635 solid oral formulation - fedSubjects will receive a single dose AZD4635 solid oral formulation after high fat meal. |
| Part B - solid oral formulation with PPI | Experimental | Drug: Lansoprazole and AZD4635 50 mg solid oral formulationSubjects will receive 30 mg lansoprazole BID and a single dose of AZD4635 solid oral formulation in the fasted state. |
| Part B - dose exploration 1 | Experimental | Drug: AZD4635 solid oral formulation - fastedIf dose adjustment is required, subjects will receive a different single dose (XX mg) of AZD4635 solid oral formulation, in the fasted state. |
| Part B - dose exploration 2 | Experimental | Drug: AZD4635 solid oral formulation - fastedIf dose adjustment is required, subjects will receive a different single dose (YY mg) of AZD4635 solid oral formulation, in the fasted state. |
| Part B - variant 1 | Experimental | Drug: AZD4635 solid oral formulation variant 1 - fasted, Drug: [14C] AZD4635 IV microtracer - fastedSubjects will receive a single dose of AZD4635 solid oral formulation, variant 1 in the fasted state and optional [14C] AZD4635 IV microtracer. |
| Part B - variant 2 | Experimental | Drug: AZD4635 solid oral formulation variant 2 - fastedSubjects will receive a single dose of AZD4635 solid oral formulation, variant 2 in the fasted state. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male subjects aged 18 to 55 years with suitable veins for cannulation or repeated venepuncture and IV infusion.
- Have a body mass index of 18.0 to 32.0 kg/m2, and weigh at least 50 kg and no more than 100 kg.
- Must be willing and able to communicate and participate in the whole study
- Must agree to adhere to the contraception requirements, as precaution should avoid fathering a child by either true abstinence or use together, with their female partner/spouse, a highly effective contraception form of birth control in combination with a barrier method, starting from the time of AZD4635 administration until 90 days after the last dose of AZD4635.
Key exclusion criteria (26 listed)
- History of any clinically significant disease or disorder which in investigator opinion, may put volunteer at risk because of participation in the study, or influence results of volunteer'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.
- Presence of refractory nausea and vomiting or chronic gastrointestinal diseases.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- Any confirmed clinically significant abnormalities in clinical chemistry, haematology or urinalysis as judged by the investigator
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 |
|---|---|---|
| AZD4635 50 mg nano-suspension (reference)Subjects will receive a single dose of AZD4635 50 mg nano-suspension (reference) in the fasted state. | Drug | Part A - nano-suspension |
| AZD4635 solid oral formulation - fastedSubjects will receive a single dose of AZD4635 solid oral formulation, in the fasted state. | Drug | Part A - solid oral formulation, Part B - dose exploration 1, Part B - dose exploration 2 |
| AZD4635 solid oral formulation - fedSubjects will receive a single dose of AZD4635 solid oral formulation, in the fed state. | Drug | Part B-solid oral formulation with food |
| Lansoprazole and AZD4635 50 mg solid oral formulationSubjects will receive lansoprazole 30 mg BID for 5 days followed by a single dose of AZD4635 50 mg solid oral formulation in the fasted state. | Drug | Part B - solid oral formulation with PPI |
| AZD4635 solid oral formulation variant 1 - fastedSubjects will receive a single dose of AZD4635 solid oral formulation, variant 1 in the fasted state. | Drug | Part B - variant 1 |
| AZD4635 solid oral formulation variant 2 - fastedSubjects will receive a single dose of AZD4635 solid oral formulation, variant 2 in the fasted state. | Drug | Part B - variant 2 |
| [14C] AZD4635 IV microtracer - fastedSubjects will receive a single dose of [14C] AZD4635 IV microtracer. This intervention will be co-administered with AZD4635 solid oral formulation variant 1. | Drug | Part B - variant 1 |
Primary outcome
Maximum observed plasma concentration (Cmax) of AZD4635 solid oral formulation and nano-suspension (reference)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Assessment of maximum concentration (Cmax) in plasma
Exposure to AZD4635 solid oral formulation and nano-suspension (reference)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Assessment of exposure through measurement of area under the curve (AUC) in plasma
17 secondary outcomes
Time to maximum concentration (tmax) of AZD4635 solid oral formulation variants 1 and 2 in plasma
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Maximum concentration (Cmax) of AZD4635 solid oral formulation variants 1 and 2 in plasma
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to time of last measurable concentration (AUClast) for AZD4635 solid oral formulation variants 1 and 2
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to 48 hours (AUC 0-48) for AZD4635 solid oral formulation variants 1 and 2
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Area under the plasma concentration-time curve from zero to infinity (AUC 0-inf.) for AZD4635 solid oral formulation variants 1 and 2
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Determine absolute bioavailability (F) of AZD4635
Time frame: Predose, 0.25h, 0.33h, 0.42h, 0.5h, 0.58h, 0.67h, 0.75h, 1h, 1.25h, 1.5h, 2h, 2.5h, 4.5h, 6.5h, 8.5h, 12.5h, 24h 48h, 72h, 96h, 120h
Time to maximum concentration (tmax) of AZD4635 solid oral formulation in plasma in fasted and fed state (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Maximum concentration (Cmax) of AZD4635 solid oral formulation in plasma in fasted and fed state (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to time of last measurable concentration (AUClast) for AZD4635 solid oral formulation in fasted and fed state (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to 48 hours (AUC 0-48) for AZD4635 solid oral formulation in fasted and fed state (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Area under the plasma concentration-time curve from zero to infinity (AUC 0-inf.) for AZD4635 solid oral formulation in fasted and fed state (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Time to maximum concentration (tmax) of AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Maximum concentration (Cmax) of AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to time of last measurable concentration (AUClast) for AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Area under the plasma concentration-time curve from zero to 48 hours (AUC 0-48) for AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Area under the plasma concentration-time curve from zero to infinity (AUC 0-inf.) for AZD4635 solid oral formulation with and without lansoprazole PPI (proton pump inhibitor) (optional)
Time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h
Number of adverse events (AE) experienced by subjects
Time frame: Approximately 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2020.
- Results of this clinical trial are available on www.astrazenecaclinicaltrials.comLink provided by the sponsor.
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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.
Sharan Sidhu, MBChB, BAO, MRCS, MFPM principal investigator
Quotient Sciences Limited (indemnified by Medical Protection Society)
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 AZD4635 50 mg nano-suspension (reference), AZD4635 solid oral formulation - fasted and AZD4635 solid oral formulation - fed in people with Healthy Volunteers, 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 5 inclusion and 26 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 7 May 2020. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum observed plasma concentration (Cmax) of AZD4635 solid oral formulation and nano-suspension (reference) (time frame: Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h). The study lists 2 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 7 May 2020.