Healthy Male SubjectsPhase 1NCT05888207
A Study to Assess the Effects of Fluvoxamine on Savolitinib Exposure in Healthy Male Subjects
A Phase 1 study testing Savolitinib and Fluvoxamine in people with Healthy Male Subjects, run by AstraZeneca at 1 site in United States.
Trial summary
This study will assess the effects of strong CYP1A2 (Cytochrome P450 1A2) inhibitor (fluvoxamine) on savolitinib exposure in healthy male subjects, performed at a single clinical unit. 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 Male Subjects
- What is being tested?
- Savolitinib and Fluvoxamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2023to 17 Aug 2023
- 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
- Healthy subjects with suitable veins for cannulation or repeated venipuncture.
- Male subjects must use barrier contraception.
- Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Regular bowel movements.
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, 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 abnormalities in clinical chemistry, hematology, or urinalysis results, vital signs, 12 lead ECG and physical examination.
- QTcF > 450 ms or QT > 500 ms or other ECG abnormality making interpretation more difficult, as judged by the investigator, or a history of additional risk factors for Torsades de Points, which in the opinion of the investigator may put the subject at risk.
- Any positive result on screening for serum hepatitis B surface antigen OR anti-HBc antibody, indicative of active hepatitis B, hepatitis C antibody, or HIV antibody.
Show all 18Show fewer
- History of latent or chronic infections.
- Known or suspected drug or alcohol abuse or positive drugs of abuse test. History of excessive alcohol assumption or chronic alcohol induced disease. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 1 month (30 days) of Visit 2 (Day -1 of Period 1) or 5 half lives whichever longer in this study or participation in a method development study (no drug) 1 month prior to Visit 2. The period of exclusion begins 1 month after the final dose or 5 half-lives after the final dose or 1 month after the last visit, whichever is the longest.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
- Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 6 months prior to screening.
- Use of any prescribed or non prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies (which include but are not limited to: kava, ephedra [ma hung], ginko biloba, dehydroepiandrosterone, yohimbe, saw palmetto and ginseng), 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 (> 5 half-lives) if the medication has a long half-life.
- Subject has clinical signs and symptoms consistent with COVID-19, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission unless confirmed by a negative SARS CoV-2 PCR test.
- History of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated).
- Excessive intake of caffeine-containing drinks or food.
- Planned in-patient surgery, dental procedure, or hospitalization during the study.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug.
- Received a seasonal flu vaccine (including H1N1, H1N5) 28 days prior to first dose of study drug.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open-label, Fixed-sequence Study to Assess the Effects of Strong CYP1A2 Inhibitor (Fluvoxamine) on Savolitinib Exposure in Healthy Male Subjects
This study will assess the effects of strong CYP1A2 (Cytochrome P450 1A2) inhibitor (fluvoxamine) on savolitinib exposure in healthy male subjects, performed at a single clinical unit.
Read the detailed description
This study will be a Phase I, open-label, fixed-sequence, 2-treatment period study.
The study will consist of 2 periods. During period 1 of the study, each subject will receive a single oral dose of savolitinib following an overnight fast. A low-fat breakfast will be provided prior to dosing. There will be a minimum washout period of 10 days (14 days between two successive savolitinib doses) between period 1 and period 2.
During period 2 of the study, subject will take oral doses of fluvoxamine alone from Days 1 to 4. There would be no dietary restrictions for fluvoxamine dosing. On Day 5, subjects will take a single oral dose of savolitinib and oral dose of fluvoxamine. On Day 6, subject will receive an oral dose of fluvoxamine alone. Each subject would be involved in the study for 9 weeks (including screening window).
- Conditions
- Healthy Male Subjects
- Being tested
- Savolitinib, Fluvoxamine
- Keywords
- Fixed-sequence, CYP1A2 inhibitor, Drug-drug interaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SavolitinibDrug
Savolitinib will be administered as a single oral dose on Day 1 of Period 1 and on Day 5 of Period 2.
FluvoxamineDrug
Only fluvoxamine will be administered as a twice daily oral dose from Days 1 to 4 of Period 2. On Day 5 of Period 2, subject will receive a twice daily oral dose of fluvoxamine along with savolitinib. On Day 6 of Period 2, subject will receive a twice daily oral dose of fluvoxamine alone.
| Study group | Role | What they receive |
|---|---|---|
| Savolitinib/Savolitinib+Fluvoxamine | Experimental | In period 1, subjects will receive a single oral dose of savolitinib on Day 1 after overnight fasting. Following minimum 10 days of washout after the last dose of savolitinib, in period 2 subjects will take oral doses of fluvoxamine alone, twice daily from Days 1 to 4. On Day 5 subject will receive a single oral dose of savolitinib and a twice daily oral dose of fluvoxamine. On Day 6, subjects will receive a twice daily oral dose of fluvoxamine alone. Receives: Drug: Savolitinib; Drug: Fluvoxamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma (peak) drug concentration (Cmax) for savolitinib
To evaluate the effects of fluvoxamine on savolitinib Cmax in healthy male subjects after administration of a single oral dose.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Area under plasma concentration time curve from zero to infinity (AUCinf) for savolitinib
To evaluate the effects of fluvoxamine on savolitinib AUCinf in healthy male subjects after administration of a single oral dose.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Secondary outcomes (14)
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) for savolitinib
To evaluate the AUClast of savolitinib when administered alone or in combination with fluvoxamine.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
AUClast for metabolites M2 and M3
To evaluate the AUClast of savolitinib metabolites (M2 and M3) when savolitinib is administered alone or in combination with fluvoxamine.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Cmax for metabolites M2 and M3
To evaluate the Cmax of savolitinib metabolites (M2 and M3) when savolitinib is administered alone or in combination with fluvoxamine.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
AUCinf for metabolites M2 and M3
To evaluate the AUCinf of savolitinib metabolites (M2 and M3) when savolitinib is administered alone or in combination with fluvoxamine.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Ratio of metabolite Cmax to parent Cmax (MRCmax)
To evaluate the MRCmax of savolitinib and its metabolites (M2 and M3) when savolitinib is administered alone.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Ratio of metabolite AUCinf to parent AUCinf (MRAUCinf)
To evaluate the MRAUCinf of savolitinib and its metabolites (M2 and M3) when savolitinib is administered alone.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Ratio of metabolite AUClast to parent AUClast (MRAUClast)
To evaluate the MRAUClast of savolitinib and its metabolites (M2 and M3) when savolitinib is administered alone.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Time to reach peak or maximum observed concentration or response following drug administration (tmax) for savolitinib and metabolites (M2 and M3)
To evaluate the tmax of savolitinib and its metabolites (M2 and M3) when savolitinib is administered alone.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t1/2λz) for savolitinib and metabolites (M2 and M3)
To evaluate the t1/2λz of savolitinib and its metabolites (M2 and M3) when savolitinib is administered alone.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Terminal rate constant, estimated by log linear least squares regression of the terminal part of the concentration time curve (λz) for savolitinib and metabolites (M2 and M3)
To evaluate the λz of savolitinib and its metabolites (M2 and M3) when savolitinib is administered alone.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Number of data points used for λz determination (λzN) for savolitinib and metabolites (M2 and M3)
To evaluate the λzN of savolitinib and its metabolites (M2 and M3) when savolitinib is administered alone.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for savolitinib
To evaluate the CL/F of savolitinib when savolitinib is administered alone.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F) for savolitinib
To evaluate the Vz/F of savolitinib when savolitinib is administered alone.
Measured: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Number of subjects with adverse events (AEs)
To assess additional safety and tolerability of savolitnib.
Measured: From screening (Day -28 to Day -2) to follow up visit (approximately 9 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2023
- Study start2 Jun 2023
- Primary completion17 Aug 2023
- Study completion17 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Male 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
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 16 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
- NCT05888207
- Sponsor's protocol ID
- D5084C00015
- Status last verified
- Aug 2023
- First submitted
- 25 May 2023
- Last updated
- 29 Aug 2023
- 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 Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Fixed-sequence Study to Assess the Effects of Strong CYP1A2 Inhibitor (Fluvoxamine) on Savolitinib Exposure in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT05888207
- Acronym / sponsor ID
- D5084C00015
- Conditions
- Healthy Male Subjects
- Keywords
- Fixed-sequence, CYP1A2 inhibitor, Drug-drug interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 2 Jun 2023 (actual)
- Primary completion
- 17 Aug 2023 (actual)
- Study completion
- 17 Aug 2023 (actual)
- First posted
- 5 Jun 2023 (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.
This study will assess the effects of strong CYP1A2 (Cytochrome P450 1A2) inhibitor (fluvoxamine) on savolitinib exposure in healthy male subjects, performed at a single clinical unit.
Detailed description
This study will be a Phase I, open-label, fixed-sequence, 2-treatment period study.
The study will consist of 2 periods. During period 1 of the study, each subject will receive a single oral dose of savolitinib following an overnight fast. A low-fat breakfast will be provided prior to dosing. There will be a minimum washout period of 10 days (14 days between two successive savolitinib doses) between period 1 and period 2.
During period 2 of the study, subject will take oral doses of fluvoxamine alone from Days 1 to 4. There would be no dietary restrictions for fluvoxamine dosing. On Day 5, subjects will take a single oral dose of savolitinib and oral dose of fluvoxamine. On Day 6, subject will receive an oral dose of fluvoxamine alone. Each subject would be involved in the study for 9 weeks (including screening window).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Savolitinib/Savolitinib+Fluvoxamine | Experimental | Drug: Savolitinib, Drug: FluvoxamineIn period 1, subjects will receive a single oral dose of savolitinib on Day 1 after overnight fasting. Following minimum 10 days of washout after the last dose of savolitinib, in period 2 subjects will take oral doses of fluvoxamine alone, twice daily from Days 1 to 4. On Day 5 subject will receive a single oral dose of savolitinib and a twice daily oral dose of fluvoxamine. On Day 6, subjects will receive a twice daily oral dose of fluvoxamine alone. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy subjects with suitable veins for cannulation or repeated venipuncture.
- Male subjects must use barrier contraception.
- Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Regular bowel movements.
Key exclusion criteria (18 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, 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 abnormalities in clinical chemistry, hematology, or urinalysis results, vital signs, 12 lead ECG and physical examination.
- QTcF > 450 ms or QT > 500 ms or other ECG abnormality making interpretation more difficult, as judged by the investigator, or a history of additional risk factors for Torsades de Points, which in the opinion of the investigator may put the subject at risk.
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 |
|---|---|---|
| SavolitinibSavolitinib will be administered as a single oral dose on Day 1 of Period 1 and on Day 5 of Period 2. | Drug | Savolitinib/Savolitinib+Fluvoxamine |
| FluvoxamineOnly fluvoxamine will be administered as a twice daily oral dose from Days 1 to 4 of Period 2. On Day 5 of Period 2, subject will receive a twice daily oral dose of fluvoxamine along with savolitinib. On Day 6 of Period 2, subject will receive a twice daily oral dose of fluvoxamine alone. | Drug | Savolitinib/Savolitinib+Fluvoxamine |
Primary outcome
Maximum observed plasma (peak) drug concentration (Cmax) for savolitinib
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
To evaluate the effects of fluvoxamine on savolitinib Cmax in healthy male subjects after administration of a single oral dose.
Area under plasma concentration time curve from zero to infinity (AUCinf) for savolitinib
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
To evaluate the effects of fluvoxamine on savolitinib AUCinf in healthy male subjects after administration of a single oral dose.
14 secondary outcomes
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) for savolitinib
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
AUClast for metabolites M2 and M3
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Cmax for metabolites M2 and M3
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
AUCinf for metabolites M2 and M3
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Ratio of metabolite Cmax to parent Cmax (MRCmax)
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Ratio of metabolite AUCinf to parent AUCinf (MRAUCinf)
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Ratio of metabolite AUClast to parent AUClast (MRAUClast)
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Time to reach peak or maximum observed concentration or response following drug administration (tmax) for savolitinib and metabolites (M2 and M3)
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t1/2λz) for savolitinib and metabolites (M2 and M3)
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Terminal rate constant, estimated by log linear least squares regression of the terminal part of the concentration time curve (λz) for savolitinib and metabolites (M2 and M3)
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Number of data points used for λz determination (λzN) for savolitinib and metabolites (M2 and M3)
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for savolitinib
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F) for savolitinib
Time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7
Number of subjects with adverse events (AEs)
Time frame: From screening (Day -28 to Day -2) to follow up visit (approximately 9 weeks)
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 29 Aug 2023.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Related trials for Healthy Male Subjects
RecruitingPhase 1
A Study to Investigate the Pharmacokinetics and Safety of PKN605 in Participants With Moderate and Severe Renal Impairment Compared to Matched Control Subjects With Normal Renal Function
Participants With Moderate and Severe Renal Impairment and Healthy Participants
RecruitingPhase 1
A Randomized, Double-Blind, Positive-Controlled, Parallel Pharmacokinetic Phase I Clinical Study of Cetuximab Injection Versus Erbitux in Healthy Male Subjects
Cetuximab, Bioequivalence
RecruitingPhase 1
Absorption, Distribution, Metabolism, and Excretion of 14C-VX-407 After a Single Oral Dose
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
RecruitingObservational study
Urinary Vitamin C Loss in Diabetic Subjects
Diabetes
Not yet recruitingPhase 1
Pharmacokinetic Characteristics, Safety, and Immunogenicity of HLX29 Compared With HLX11
Health Adult Subjects
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.
The record lists no contact. Use the official record to reach the sponsor.
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 Savolitinib and Fluvoxamine in people with Healthy Male Subjects, run by AstraZeneca at 1 site in United States.
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 4 inclusion and 18 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 29 Aug 2023. 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 States. 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 (peak) drug concentration (Cmax) for savolitinib (time frame: Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7). 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 29 Aug 2023.