Solid and Hematological MalignanciesPhase 1NCT04944771
Study to Assess the Effect of Food and Acid Reducing Agents on the Absorption of Capivasertib in Healthy Participants
A Phase 1 study testing Capivasertib and Rabeprazole in people with Solid and Hematological Malignancies, run by AstraZeneca at 1 site in Germany.
Trial summary
This is a two-part, open-label, randomized, crossover study in healthy subjects (vasectomized males and women of non-childbearing potential), performed at 2 study centers Read more about this study
- Who is it for?
- Ages 18 to 58 yearsHealthy volunteers can take part
- Conditions the study is for
- Solid and Hematological Malignancies
- What is being tested?
- Capivasertib and Rabeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteGermany
- Study dates
- 26 Jul 2021to 4 May 2022
- Phase
- Phase 1
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 58 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 female subjects aged 18 to 58 years with suitable veins for cannulation or repeated venipuncture.
- Females must not be lactating and must be of non-childbearing potential, confirmed at screening:
- Postmenopausal defined as aged > 40 years and amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone levels in the postmenopausal range.
- Documentation of irreversible/permanent surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation, at least 6 months prior to screening.
- Male subjects must be vasectomized, at least 6 months prior to screening, with documented post-procedural medical assessment of surgical success.
- Have a body mass index between 18.0 and 29.9 kg/m^2 (inclusive) for males and 18 to 32 kg/m^2 (inclusive) for females; and weigh at least 50 kg and no more than 100 kg inclusive.
- Non-smoker, defined as a subject who has not smoked previously or who has discontinued smoking.
Who cannot join
- History of any clinically significant disease or disorder.
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
- Any clinically significant abnormal findings in vital signs at screening and/or admission to the study center.
- Clinically significant abnormalities in glucose metabolism defined by any of the following:
- Diagnosis of diabetes mellitus type I or II (irrespective of management).
Show all 19Show fewer
- Blood glucose value ≥ 5.9 mmol/L after fasting for at least 8 hours, at screening or on admission to study center.
- Glycosylated hemoglobin > upper limit of normal (up to 6.2% [44 mmol/mol]).
- Any positive result on screening for serum hepatitis B surface antigen or antibody to hepatitis B core antigen, hepatitis C antibody, and human immunodeficiency virus antibody.
- Known or suspected history of drug abuse.
- Has received another new chemical entity within 3 months of the first administration of IMP in this study.
- Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL 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 capivasertib, rabeprazole, or famotidine.
- Subjects who have previously received capivasertib.
- Subject has a positive test result for Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction on admission.
- Subject has clinical signs and symptoms consistent with Coronavirus Disease 2019 (COVID-19) (eg, fever, dry cough, dyspnea, sore throat, anosmia/hyposmia, loss or reduced taste, and fatigue) or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
- History of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated).
- Subjects who are regularly exposed to the risk of COVID-19 infection as part of their daily life (eg, health care professionals working in COVID-19 wards or at emergency departments).
- Subjects who have had a COVID-19 vaccine within 3 weeks prior to screening or are planning to get a COVID-19 vaccine during the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Randomized, Crossover Study in Healthy Subjects to Evaluate the Effect of Food and Acid Reducing Agent(s) on the Pharmacokinetics of Capivasertib
This is a two-part, open-label, randomized, crossover study in healthy subjects (vasectomized males and women of non-childbearing potential), performed at 2 study centers
Read the detailed description
Part 1 of the study will comprise:
- A screening period of maximum 28 days.
- Three treatment periods [Treatment A: Single oral dose of capivasertib in overnight fasted state, Treatment B:Single oral dose of capivasertib in fed state (high-fat, high-calorie breakfast) and Treatment C:Twice daily oral doses of rabeprazole for 3 days and a single dose on Day 1, and a single oral dose of capivasertib in fasted conditions] during which subjects will be resident from the morning of Day -1 (Day -4 for subjects receiving rabeprazole [Treatment C]) and discharged after the last pharmacokinetic (PK) sample collection, 48 hours after dosing of capivasertib of each treatment period.
- A final visit 7 to 14 days after the last capivasertib PK sample in Treatment Period 3.
Part 2 of the study will only be initiated if the findings from Part 1 show an interaction or are inconclusive. Part 2 of the study will comprise:
- A screening period of at least 28 days.
- Three treatment periods [Any 3 treatments: Treatment D:Single oral dose of capivasertib in overnight fasted state, Treatment E: Single oral dose of capivasertib in fed state (low-fat, low-calorie breakfast), Treatment F: Single oral dose of capivasertib in partially fasted conditions (food restricted from 2 hours prior to dosing until 1 hour after dosing), Treatment G: Single oral dose of capivasertib and single dose of famotidine in fasted condition and Treatment H: Twice daily oral doses of rabeprazole for 3 days (Days -3 to -1) and a single oral dose of capivasertib in fed state] during which subjects will be resident from the morning of Day -1 (Day -4 for subjects receiving rabeprazole [Treatment H]) and will be discharged after the last PK sample collection 48 hours after dosing of capivasertib of each treatment period.
- A final visit 7 to 14 days after the last capivasertib PK sample in Treatment Period 3.
The interim results from Part 1 indicated a potentially clinically relevant food interaction only and therefore Treatments D, E, and F will be studied in Part 2.
- Conditions
- Solid and Hematological Malignancies
- Being tested
- Capivasertib, Rabeprazole
- Keywords
- Crossover, Acid reducing agent, Food effect, Pharmacokinetics, Serine/threonine specific protein kinase inhibitor
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapivasertibDrug
Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F.
RabeprazoleDrug
Participants will receive twice daily oral doses of rabeprazole for 3 days (Days -3 to -1) and a single dose on the morning of Day 1 for Treatment C.
| Study group | Role | What they receive |
|---|---|---|
| Treatment ABC | Experimental | Participants will be randomized to receive oral doses of Treatment A, Treatment B and Treatment C. Receives: Drug: Capivasertib; Drug: Rabeprazole |
| Treatment ACB | Experimental | Participants will be randomized to receive oral doses of Treatment A, Treatment C and Treatment B. Receives: Drug: Capivasertib; Drug: Rabeprazole |
| Treatment BAC | Experimental | Participants will be randomized to receive oral doses of Treatment B, Treatment A and Treatment C. Receives: Drug: Capivasertib; Drug: Rabeprazole |
| Treatment BCA | Experimental | Participants will be randomized to receive oral doses of Treatment B, Treatment C and Treatment A. Receives: Drug: Capivasertib; Drug: Rabeprazole |
| Treatment CAB | Experimental | Participants will be randomized to receive oral doses of Treatment C, Treatment A and Treatment B. Receives: Drug: Capivasertib; Drug: Rabeprazole |
| Treatment CBA | Experimental | Participants will be randomized to receive oral doses of Treatment C, Treatment B and Treatment A. Receives: Drug: Capivasertib; Drug: Rabeprazole |
| Treatment DEF | Experimental | Participants will be randomized to receive oral doses of Treatment D, Treatment E and Treatment F. Receives: Drug: Capivasertib |
| Treatment DFE | Experimental | Participants will be randomized to receive oral doses of Treatment D, Treatment F and Treatment E. Receives: Drug: Capivasertib |
| Treatment EDF | Experimental | Participants will be randomized to receive oral doses of Treatment E, Treatment D and Treatment F. Receives: Drug: Capivasertib |
| Treatment EFD | Experimental | Participants will be randomized to receive oral doses of Treatment E, Treatment F and Treatment D. Receives: Drug: Capivasertib |
| Treatment FDE | Experimental | Participants will be randomized to receive oral doses of Treatment F, Treatment D and Treatment E. Receives: Drug: Capivasertib |
| Treatment FED | Experimental | Participants will be randomized to receive oral doses of Treatment F, Treatment E and Treatment D. Receives: Drug: Capivasertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax of Capivasertib
Maximum observed plasma (peak) drug concentration (Cmax) of capivasertib when administered alone under fed and fasted conditions, and in combination with acid reducing agent(s) rabeprazole and famotidine (if required).
Measured: Part 1 and Part 2: From Day 1 to Day 3
AUCinf of Capivasertib
Area under plasma concentration time curve from zero to infinity (AUCinf) of capivasertib when administered alone under fed and fasted conditions, and in combination with acid reducing agent(s) rabeprazole and famotidine (if required).
Measured: Part 1 and Part 2: From Day 1 to Day 3
AUClast of Capivasertib
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of capivasertib when administered alone under fed and fasted conditions, and in combination with acid reducing agent(s) rabeprazole and famotidine (if required).
Measured: Part 1 and Part 2: From Day 1 to Day 3
Secondary outcomes (1)
Number of participants with serious and non-serious adverse events
Safety and tolerability of capivasertib when administered alone under fed and fasted conditions, and in combination with acid reducing agent(s) rabeprazole and famotidine (if required).
Measured: Part 1: From Screening (Day -28 to Day -5) upto Follow-up Visit/Early Termination (7 to 14 days); Part 2: From Screening (Day -28 to Day -2) upto Follow-up Visit/Early Termination (7 to 14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2021
- Study start26 Jul 2021
- Primary completion4 May 2022
- Study completion4 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid and Hematological MalignanciesStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04944771
- Sponsor's protocol ID
- D3614C00005
- Other IDs
- 2021-000836-74
- Status last verified
- May 2022
- First submitted
- 28 Jun 2021
- Last updated
- 9 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.