A Pharmacokinetic and Bioequivalence Study of Savolitinib Tablets in Healthy Chinese Male Volunteers

May 15, 2019 updated by: Hutchison Medipharma Limited

A Randomized, Open-label, Crossover Pharmacokinetic and Bioequivalence Study of Savolitinib Tablets Produced by Two Different Processes in Healthy Chinese Male Volunteers

This is a single-center, randomized, open lebal, single-dose, three-period, crossover clinical study in healthy Chinese male subjects to assess the pharmacokinetics and bioequivalence/bioavailability of two formulation savolitinib tablets.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Thirty six Chinese male subjects who met the inclusion criteria but not met the exclusion criteria, will be hospitalized in Phase I Ward one day before first dosing and randomized into three groups, 12 subjects each, at a ratio of 1:1:1. The subjects in the different group will follow the fixed dosing regimen with 600 mg savolitinib tablets (200 mg/tablet x 3 tablets) after the standard meal on day 1 in cycle 1, 2 and 3 respectively: TRR, RTR or RRT, where "T" indicates dry granulation savolitinib tablet and "R" indicates wet granulation savolitinib tablet. PK blood samples, 2 mL each time, will be collected at the following time points in each dosing cycle: within 0.5 hours before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 36, 48 hours after dosing(16 time-points).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200031
        • Shanghai Xuhui District Central Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 40 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  1. Subjects must agree to comply with the protocol and Informed consent must be obtained in writing for all subjects;
  2. Healthy male subjects aged 18 to 45 years inclusive at the time of screening;
  3. Weight ≥ 50 kg, body mass index (BMI) of 19-26 kg/m2;
  4. No clinically significant abnormalities or findings in medical history, vital signs, physical examination, 12-lead ECG and laboratory values;
  5. Males with the ability to have children must commit to adopting reliable contraceptive measures (e.g. condoms, contraceptive sponges, contraceptive gels, contraceptive films, intrauterine devices, contraceptives for oral or injectable intake, subcutaneous implants or other contraceptives) in collaboration with their partners for the duration of the study and for three months after the final dosage.

Exclusion Criteria:

  1. History or symptoms of a clinically significant illness in metabolic/ endocrine, liver, kidney, blood, lung, immune system, cardiovascular, gastrointestinal, genitourinary, neurological, or psychiatric systerm in the 3 months before the study, as determined by the investigator;
  2. History of gastrointestinal surgery, kidney surgery and cholecystectomy, which may potentially affect the absorption or excretion of drugs, as determined by the investigator ;
  3. History of a severe allergy (for example, certain drug allergy) and acute allergic rhinitis or food allergy within 2 weeks prior to the screening stage;
  4. Serum albumin < 35 g/L;
  5. Hypertention: systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg
  6. Mean corrected QT interval (QTcF) in electrocardiograms (ECG), males > 450 milliseconds, or existing factors that may increase the risk of QTc prolongation, such as chronic hypokalemia that cannot be corrected by potassium supplementation, or congenital or familial long QT syndrome or a family history of unexplained sudden death under 40 years of age in first-degree relatives, or use any combination of drugs known to prolong the QT interval and cause torsades de pointes.
  7. Clinical significant abormal findings in Chest X-ray (posteroanterior position) examination;
  8. Serum virology positive findings, including HBS Ag, HCV Ab, HIV Ab, or TP Ab;
  9. Current smoker of more than 10 cigarettes or equivalent / day during past 3 month prior to commencing the study and unable to completely stop smoking during the study;
  10. Have blood or blood products transfusion within 2 months; or blood donation of more than 250 mL within 1 month or 400 mL within 3 months prior to screening; or planning to donate blood or blood components during the study or within 1 month after the end of the study;
  11. History of alcohol abuse or drug addiction within one year prior to screening;
  12. Participation in any other investigational drug clinical study while last dose was administrated within three months prior to the screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Savolitinib Test Preparation
The subjects in this arm will receive Test preparation (T). T is dry granulation savolitinib tablets.
Drug: Savolitinib Test Preparation
Test preparation (T): dry granulation savolitinib tablets.
Other Names:
  • HMPL-504, volitinib, AZD6094
Experimental: Savolitinib Reference Preparation
The subjects in this arm will receive Reference preparation(R). R is wet granulation savolitinib tablets.
Drug: Savolitinib Reference Preparation
Reference preparation (R): wet granulation savolitinib tablets.
Other Names:
  • HMPL-504, volitinib, AZD6094

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The area under the curve(AUC) of savolitinib
Time Frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration.
Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
Maximum observed plasma concentration (Cmax) of savolitinib
Time Frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
Maximum observed concentration, occurring at Tmax.
Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
The time to Cmax (peak time, Tmax) of savolitinib
Time Frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
The time at which maximum plasma concentration (Cmax) is observed.
Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
Half-life (t1/2) of savolitinib
Time Frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
The time required for the concentration of the drug to reach half of its original value.
Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
Bioequivalence of savolitinib
Time Frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
A term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug.
Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To observe the safety of healthy volunteers after a single oral dose of savolitinib
Time Frame: From the first dose to within 12 days after the last dose
Incidence of adverse events evaluated by NCI CTCAE v4.03
From the first dose to within 12 days after the last dose
Relative bioavailability of savolitinib
Time Frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
The area under the curve (AUC) is the definite integral in a plot of drug concentration in blood plasma vs. time.
Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hutchison Medipharma Limited

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jingying Jia, Shanghai Xuhui District Central Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 16, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 2, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 14, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 25, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 4, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 16, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2019

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2018-504-00CH1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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