Healthy Male SubjectsPhase 1NCT05768360
A Study to Assess the Effects of Savolitinib on the Pharmacokinetics of Digoxin, Rosuvastatin, Metformin, and Furosemide in Healthy Male Subjects
A Phase 1 study testing Savolitinib, Digoxin and Metformin Hydrochloride in people with Healthy Male Subjects, run by AstraZeneca at 1 site in Germany.
Trial summary
This study will assess the effects of savolitinib on the pharmacokinetics (PK) of substrates of human transporters digoxin (P-gp), rosuvastatin (OATP1B1/3), metformin (OCT2, MATE1/2K), and furosemide (OAT1/3) 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, Digoxin and Metformin Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteGermany
- Study dates
- 25 Apr 2023to 24 Jun 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
- Male subjects must use barrier contraception (condoms) during sexual intercourse with a female partner of childbearing potential during the study and for 6 months after the last dose of the IMPs investigational medical products (IMPs).
- Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Regular bowel movements (ie, on average production of at least 1 stool per day).
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 abnormalities in clinical chemistry, hematology, or urinalysis results.
- Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening and/or first admission to the clinical unit, as judged by the investigator.
- 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 (eg heart failure, hypokalemia, family history of long QT syndrome), 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 (ie, subjects with positive anti-HBc antibody result are acceptable if anti HBc IgM antibodies are negative), hepatitis C antibody, and HIV antibody.
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- History of latent or chronic infections (eg, tuberculosis, recurrent sinusitis, genital herpes, urinary tract infections) or at risk of infection.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months (12 weeks) or within 5 half-lives of the drug, whichever is longer, of Visit 2 (Day -1 of Period 1) in this study or participation in a method development study (no drug) 1 month prior to Visit 2. The period of exclusion ends 3 months after the final dose or after 5 elimination half-lives of the drug or 1 month after the last visit, whichever is the longer.
- 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 savolitinib, or drug cocktail medications or their excipients.
- Subject has clinical signs and symptoms consistent with Coronavirus disease (COVID-19), eg, fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission unless confirmed by a negative severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test (SARS-CoV-2 PCR test).
- Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- Positive screen for drugs of abuse or cotinine at screening or on each admission to the clinical unit or positive screen for alcohol on each admission to the clinical unit.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Fixed-sequence, Open-label Study to Assess the Effects of Savolitinib on the Pharmacokinetics of Substrates of Human Transporters Digoxin (P-gp), Rosuvastatin (OATP1B1/3), Metformin (OCT2, MATE1/2K), and Furosemide (OAT1/3) in Healthy Male Subjects
This study will assess the effects of savolitinib on the pharmacokinetics (PK) of substrates of human transporters digoxin (P-gp), rosuvastatin (OATP1B1/3), metformin (OCT2, MATE1/2K), and furosemide (OAT1/3) in healthy male subjects, performed at a single clinical unit.
Read the detailed description
This study will be performed at a single clinical unit.
Subjects will be admitted to the clinical unit on Day -1 of Period 1 and Period 2. Subjects will have a washout period of 14 days between Period 1 and Period 2.
Period 1: Subjects will recieve a single dose of a drug cocktail of 4 medications (digoxin Dose B, furosemide Dose C, metformin hydrochloride Dose D, and rosuvastatin Dose E).
Period 2: Participants will receive savolitinib (Dose A) in combination with the drug cocktail of 4 medications as received in Period 1.
The study will consist of 4 visits:
Visit 1 (Enrollment): Following full written informed consent, subjects will be screened for eligibility.
Visit 2 (Period 1: Treatment and Sample Collection Period): Each subject will be admitted to the clinical unit on Day -1 of Period 1, single dose of drug cocktail is administered on Day 1, and remain in clinical unit until Day 5 assessments. A washout period of 14 days is followed.
Visit 3 (Period 2: Treatment and Sample Collection Period): Each subject will be admitted to the clinical unit on Day -1 of Period 2, single dose of savolitinib and drug cocktail is administered, and remain in clinical unit until Day 5 assessments.
Visit 4 (Follow-up): Subjects will attend the clinical unit for a final Follow-up Visit 5 to 7 days post Day 5 in Period 2.
Each subject will be involved in the study for 9 weeks including screening to final follow up.
- Conditions
- Healthy Male Subjects
- Being tested
- Savolitinib, Digoxin, Metformin Hydrochloride, Rosuvastatin, Furosemide
- Keywords
- Drug-Drug Interaction, Substrate of human drug transporters, Fixed-sequence, Drug cocktail
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SavolitinibDrug
The subjects will receive single dose of oral film-coated tablet of Savolitinib A dose on Day 1 of Period 2 within 25 minutes [+ 5 minutes] from the start of meal.
DigoxinDrug
The subjects will receive single dose of oral uncoated tablet of Digoxin Dose B on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal.
Metformin HydrochlorideDrug
The subjects will receive single dose of oral film-coated tablet of Metformin Hydrochloride Dose D on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal.
RosuvastatinDrug
The subjects will receive single dose of oral film-coated tablet of Rosuvastatin Dose E on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal.
FurosemideDrug
The subjects will receive single dose of oral solution of Furosemide Dose C on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal.
| Study group | Role | What they receive |
|---|---|---|
| Drug cocktail/Savolitinib + Drug cocktail | Experimental | Subjects will receive two different interventions in two periods (Periods 1 and 2). In Period 1, the subjects will receive a single-dose of Drug cocktail components (digoxin Dose B, furosemide Dose C, metformin hydrochloride Dose D, and rosuvastatin Dose E). During Period 2, the subjects will receive savolitinib dose A in combination with the Drug cocktail components. Receives: Drug: Savolitinib; Drug: Digoxin; Drug: Metformin Hydrochloride; Drug: Rosuvastatin; Drug: Furosemide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Area Under Concentration-time Curve from zero to infinity (AUCinf) of the drug cocktail components
To evaluate AUCinf of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2)
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma Area under the concentration-curve from zero to the last quantifiable concentration (AUClast) of the drug cocktail components
To evaluate AUClast of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2)
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma partial area under the concentration-time curve from time 0 to time t post-dose (AUC(0-t)) of the drug cocktail components
To evaluate (AUC(0-t)) of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Maximum observed plasma drug concentration (Cmax) of drug cocktail components
To evaluate Cmax of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
The ratio of plasma AUCinf (R AUCinf) of the drug cocktail components in the presence and absence of savolitinib
To evaluate AUCinf ratio of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
The ratio of plasma AUC(0-t) (R AUC(0-t)) of the drug cocktail components in the presence and absence of savolitinib
To evaluate AUC(0-t) ratio of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
The ratio of plasma Cmax (R Cmax) of drug cocktail components in the presence and absence of savolitinib
To evaluate Cmax ratio of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Secondary outcomes (21)
Number of participants with adverse events
To assess safety and tolerability of savolitinib following oral dosing.
Measured: Day 1 in Periods 1 (Week 1) and 2 (Week 4) to Day 7 (follow-up after last Pharmacokinetic (PK) sample)
Area under plasma concentration-time curve from zero to infinity (AUCinf) of savolitinib and its metabolites (M2 and M3)
To assess AUCinf of savolitinib and its metabolites (M2 and M3).
Measured: Day 1 and Day 2 in Period 2 (Week 4)
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUCinflast) of savolitinib and its metabolites (M2 and M3)
To assess AUClast of savolitinib and its metabolites (M2 and M3)
Measured: Day 1 and Day 2 in Period 2 (Week 4)
Partial area under the concentration-time curve from time 0 to time t post-dose (AUC(0-t)) of savolitinib and its metabolites (M2 and M3)
To assess AUC(0-t) of savolitinib and its metabolites (M2 and M3).
Measured: Day 1 and Day 2 in Period 2 (Week 4)
Maximum observed plasma (peak) drug concentration (Cmax) of savolitinib and its metabolites (M2 and M3) of savolitinib and its metabolites (M2 and M3)
To assess Cmax of savolitinib and its metabolites (M2 and M3).
Measured: Day 1 and Day 2 in Period 2 (Week 4)
Observed lowest concentration before the next dose is administered (Ctrough) of savolitinib and its metabolites (M2 and M3)
To assess Ctrough of savolitinib and its metabolites (M2 and M3).
Measured: Day 1 and Day 2 in Period 2 (Week 4)
Terminal elimination half-life (t½λz) of savolitinib and its metabolites (M2 and M3)
To assess t½λz of savolitinib and its metabolites (M2 and M3).
Measured: Day 1 and Day 2 in Period 2 (Week 4)
Time to reach maximum observed concentration (tmax) of savolitinib and its metabolites (M2 and M3)
To assess tmax of savolitinib and its metabolites (M2 and M3).
Measured: Day 1 and Day 2 in Period 2 (Week 4)
Apparent volume of distribution based on the terminal phase (Vz/F) of savolitinib and its metabolites (M2 and M3)
To assess Vz/F of savolitinib and its metabolites (M2 and M3).
Measured: Day 1 and Day 2 in Period 2 (Week 4)
Apparent total body clearance (CL/F) of savolitinib and its metabolites (M2 and M3)
To assess CL/F of savolitinib and its metabolites (M2 and M3).
Measured: Day 1 and Day 2 in Period 2 (Week 4)
Maximum observed plasma (peak) drug concentration (Cmax) of cocktail parent components
To assess the Cmax of the drug cocktail parent components.
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Time to reach maximum observed plasma concentration (Tmax) of the cocktail parent components
To assess the PK parameter tmax of the drug cocktail parent components
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma terminal elimination half-life (t½λz) of cocktail parent components
To assess the PK parameter t½λz of the drug cocktail parent components.
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz) of cocktail parent components
To assess the PK parameter λz of the drug cocktail parent components.
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma Apparent total body clearance (CL/F) of cocktail parent components
To assess the PK parameter CL/F of the drug cocktail parent components.
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma Apparent volume of distribution based on the terminal phase (Vz/F) of cocktail parent components
To assess the PK parameter Vz/F of the drug cocktail parent components.
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Renal clearance (CLR) of cocktail parent components
To assess the urine PK parameter CLR of the drug cocktail parent components.
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Cumulative amount of unchanged drug excreted into urine (Ae) of cocktail parent components
To assess the urine PK parameter Ae of the drug cocktail parent components.
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae(0-t)) of cocktail parent components
To assess Ae(0-t) of the drug cocktail parent components
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Percentage of dose excreted unchanged in urine from time 0 to t (fe(0-t)) of cocktail parent components
To assess fe(0-t) of the drug cocktail parent components.
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Cumulative amount of unchanged drug excreted into urine (CumAe) of the cocktail parent components
To assess CumAe of the drug cocktail parent components
Measured: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2023
- Study start25 Apr 2023
- Primary completion24 Jun 2023
- Study completion24 Jun 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
- 6 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
- NCT05768360
- Sponsor's protocol ID
- D5084C00014
- Other IDs
- 2022-003785-21
- Status last verified
- Jul 2023
- First submitted
- 3 Mar 2023
- Last updated
- 13 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- 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 request 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.
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Fixed-sequence, Open-label Study to Assess the Effects of Savolitinib on the Pharmacokinetics of Substrates of Human Transporters Digoxin (P-gp), Rosuvastatin (OATP1B1/3), Metformin (OCT2, MATE1/2K), and Furosemide (OAT1/3) in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT05768360
- Acronym / sponsor ID
- D5084C00014
- Conditions
- Healthy Male Subjects
- Keywords
- Drug-Drug Interaction, Substrate of human drug transporters, Fixed-sequence, Drug cocktail
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 25 Apr 2023 (actual)
- Primary completion
- 24 Jun 2023 (actual)
- Study completion
- 24 Jun 2023 (actual)
- First posted
- 14 Mar 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 savolitinib on the pharmacokinetics (PK) of substrates of human transporters digoxin (P-gp), rosuvastatin (OATP1B1/3), metformin (OCT2, MATE1/2K), and furosemide (OAT1/3) in healthy male subjects, performed at a single clinical unit.
Detailed description
This study will be performed at a single clinical unit.
Subjects will be admitted to the clinical unit on Day -1 of Period 1 and Period 2. Subjects will have a washout period of 14 days between Period 1 and Period 2.
Period 1: Subjects will recieve a single dose of a drug cocktail of 4 medications (digoxin Dose B, furosemide Dose C, metformin hydrochloride Dose D, and rosuvastatin Dose E).
Period 2: Participants will receive savolitinib (Dose A) in combination with the drug cocktail of 4 medications as received in Period 1.
The study will consist of 4 visits:
Visit 1 (Enrollment): Following full written informed consent, subjects will be screened for eligibility.
Visit 2 (Period 1: Treatment and Sample Collection Period): Each subject will be admitted to the clinical unit on Day -1 of Period 1, single dose of drug cocktail is administered on Day 1, and remain in clinical unit until Day 5 assessments. A washout period of 14 days is followed.
Visit 3 (Period 2: Treatment and Sample Collection Period): Each subject will be admitted to the clinical unit on Day -1 of Period 2, single dose of savolitinib and drug cocktail is administered, and remain in clinical unit until Day 5 assessments.
Visit 4 (Follow-up): Subjects will attend the clinical unit for a final Follow-up Visit 5 to 7 days post Day 5 in Period 2.
Each subject will be involved in the study for 9 weeks including screening to final follow up.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drug cocktail/Savolitinib + Drug cocktail | Experimental | Drug: Savolitinib, Drug: Digoxin, Drug: Metformin Hydrochloride, Drug: Rosuvastatin, Drug: FurosemideSubjects will receive two different interventions in two periods (Periods 1 and 2). In Period 1, the subjects will receive a single-dose of Drug cocktail components (digoxin Dose B, furosemide Dose C, metformin hydrochloride Dose D, and rosuvastatin Dose E). During Period 2, the subjects will receive savolitinib dose A in combination with the Drug cocktail components. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Male subjects must use barrier contraception (condoms) during sexual intercourse with a female partner of childbearing potential during the study and for 6 months after the last dose of the IMPs investigational medical products (IMPs).
- Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Regular bowel movements (ie, on average production of at least 1 stool per day).
Key exclusion criteria (12 listed)
- 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 abnormalities in clinical chemistry, hematology, or urinalysis results.
- Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening and/or first admission to the clinical unit, as judged by the investigator.
- 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 (eg heart failure, hypokalemia, family history of long QT syndrome), 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 |
|---|---|---|
| SavolitinibThe subjects will receive single dose of oral film-coated tablet of Savolitinib A dose on Day 1 of Period 2 within 25 minutes [+ 5 minutes] from the start of meal. | Drug | Drug cocktail/Savolitinib + Drug cocktail |
| DigoxinThe subjects will receive single dose of oral uncoated tablet of Digoxin Dose B on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal. | Drug | Drug cocktail/Savolitinib + Drug cocktail |
| Metformin HydrochlorideThe subjects will receive single dose of oral film-coated tablet of Metformin Hydrochloride Dose D on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal. | Drug | Drug cocktail/Savolitinib + Drug cocktail |
| RosuvastatinThe subjects will receive single dose of oral film-coated tablet of Rosuvastatin Dose E on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal. | Drug | Drug cocktail/Savolitinib + Drug cocktail |
| FurosemideThe subjects will receive single dose of oral solution of Furosemide Dose C on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal. | Drug | Drug cocktail/Savolitinib + Drug cocktail |
Primary outcome
Plasma Area Under Concentration-time Curve from zero to infinity (AUCinf) of the drug cocktail components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
To evaluate AUCinf of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2)
Plasma Area under the concentration-curve from zero to the last quantifiable concentration (AUClast) of the drug cocktail components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
To evaluate AUClast of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2)
Plasma partial area under the concentration-time curve from time 0 to time t post-dose (AUC(0-t)) of the drug cocktail components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
To evaluate (AUC(0-t)) of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
Maximum observed plasma drug concentration (Cmax) of drug cocktail components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
To evaluate Cmax of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
The ratio of plasma AUCinf (R AUCinf) of the drug cocktail components in the presence and absence of savolitinib
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
To evaluate AUCinf ratio of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
The ratio of plasma AUC(0-t) (R AUC(0-t)) of the drug cocktail components in the presence and absence of savolitinib
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
To evaluate AUC(0-t) ratio of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
The ratio of plasma Cmax (R Cmax) of drug cocktail components in the presence and absence of savolitinib
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
To evaluate Cmax ratio of drug cocktail components when administered alone (period 1) and in combination with savolitinib (period 2).
21 secondary outcomes
Number of participants with adverse events
Time frame: Day 1 in Periods 1 (Week 1) and 2 (Week 4) to Day 7 (follow-up after last Pharmacokinetic (PK) sample)
Area under plasma concentration-time curve from zero to infinity (AUCinf) of savolitinib and its metabolites (M2 and M3)
Time frame: Day 1 and Day 2 in Period 2 (Week 4)
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUCinflast) of savolitinib and its metabolites (M2 and M3)
Time frame: Day 1 and Day 2 in Period 2 (Week 4)
Partial area under the concentration-time curve from time 0 to time t post-dose (AUC(0-t)) of savolitinib and its metabolites (M2 and M3)
Time frame: Day 1 and Day 2 in Period 2 (Week 4)
Maximum observed plasma (peak) drug concentration (Cmax) of savolitinib and its metabolites (M2 and M3) of savolitinib and its metabolites (M2 and M3)
Time frame: Day 1 and Day 2 in Period 2 (Week 4)
Observed lowest concentration before the next dose is administered (Ctrough) of savolitinib and its metabolites (M2 and M3)
Time frame: Day 1 and Day 2 in Period 2 (Week 4)
Terminal elimination half-life (t½λz) of savolitinib and its metabolites (M2 and M3)
Time frame: Day 1 and Day 2 in Period 2 (Week 4)
Time to reach maximum observed concentration (tmax) of savolitinib and its metabolites (M2 and M3)
Time frame: Day 1 and Day 2 in Period 2 (Week 4)
Apparent volume of distribution based on the terminal phase (Vz/F) of savolitinib and its metabolites (M2 and M3)
Time frame: Day 1 and Day 2 in Period 2 (Week 4)
Apparent total body clearance (CL/F) of savolitinib and its metabolites (M2 and M3)
Time frame: Day 1 and Day 2 in Period 2 (Week 4)
Maximum observed plasma (peak) drug concentration (Cmax) of cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Time to reach maximum observed plasma concentration (Tmax) of the cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma terminal elimination half-life (t½λz) of cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz) of cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma Apparent total body clearance (CL/F) of cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Plasma Apparent volume of distribution based on the terminal phase (Vz/F) of cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Renal clearance (CLR) of cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Cumulative amount of unchanged drug excreted into urine (Ae) of cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae(0-t)) of cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Percentage of dose excreted unchanged in urine from time 0 to t (fe(0-t)) of cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
Cumulative amount of unchanged drug excreted into urine (CumAe) of the cocktail parent components
Time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)
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 13 Jul 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. All request 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.
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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.
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, Digoxin and Metformin Hydrochloride in people with Healthy Male Subjects, run by AstraZeneca at 1 site in Germany.
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 3 inclusion and 12 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 13 Jul 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 Germany. 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?
Plasma Area Under Concentration-time Curve from zero to infinity (AUCinf) of the drug cocktail components (time frame: Day 1 to Day 5 in Periods 1 (Week 1) and 2 (Week 4)). The study lists 7 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 13 Jul 2023.