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出境医 / 临床实验 / The Effect of CS-3150 Exposure on Corrected QT (QTc) Interval Duration in Healthy Volunteers

The Effect of CS-3150 Exposure on Corrected QT (QTc) Interval Duration in Healthy Volunteers

Study Description
Brief Summary:
This study will test if a study drug (CS-3150) will affect the heart rate in healthy males and females. Two doses of the study drug will be tested. Heart rate is not expected to be different between the study groups.

Condition or disease Intervention/treatment Phase
Hypertension Mineralocorticoid Receptor Antagonist Drug: CS-3150 Drug: Moxifloxacin Drug: Placebo matching moxifloxacin tablet Drug: Placebo matching CS-3150 Phase 1

Detailed Description:
This study will assess the effect of therapeutic and supratherapeutic plasma exposures of CS-3150 on the corrected QT (QTc) interval duration after administration of single oral 10-mg and 40-mg doses of CS-3150 in healthy male and female participants. This study will also determine the safety and tolerability of CS-3150 administration, assess the effect on electrocardiogram (ECG) parameters, detect QT interval (QT)/QTc prolongation with a positive control (moxifloxacin), characterize pharmacokinetics (PK) of CS-3150, and assess exposure-response relationship of CS-3150 on QTc.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

This is a phase 1, single center, randomized, single-dose, double-blind, double-dummy, placebo- and positive-controlled, 4-period crossover study. Participants will be randomized to one of the following 4 treatment sequences:

  1. CS-3150 (10-mg dose)/CS-3150 (40-mg dose)/moxifloxacin/placebo
  2. CS-3150 (40-mg dose)/placebo/CS-3150 (10-mg dose)/moxifloxacin
  3. Moxifloxacin/CS-3150 (10-mg dose)/placebo/CS-3150 (40-mg dose)
  4. Placebo/moxifloxacin/CS-3150 (40-mg dose)/CS-3150 (10-mg dose)
Masking: Double (Participant, Investigator)
Masking Description: The Investigator, participants, and all other clinical management and personnel will be blinded to treatment. CS-3150 and moxifloxacin (positive control) treatments will be blinded by matching placebos.
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind, Single-Dose, Placebo- and Positive-Controlled Crossover Study to Evaluate the Effect of Therapeutic and Supratherapeutic Exposure to CS-3150 on QTc Interval Duration in Healthy Male and Female Subjects
Actual Study Start Date : November 19, 2015
Actual Primary Completion Date : December 23, 2015
Actual Study Completion Date : December 23, 2015
Arms and Interventions
Arm Intervention/treatment
Experimental: 10 mg CS-3150 (Treatment Sequence 1)
Participants will receive the following treatment sequence (1 treatment per Period): a single oral 10-mg dose of CS-3150, a 40-mg dose of CS-3150, a 400-mg dose of moxifloxacin, followed by placebo.
 Drug: CS-3150
Single, oral administration; 10-mg or 40-mg dose
Other Name: Esaxerenone

Drug: Moxifloxacin
Single, oral administration; 400 mg-tablet
Other Name: Avelox

Drug: Placebo matching moxifloxacin tablet
Placebo tablets matching moxifloxacin tablets
Other Name: Placebo
Experimental: 40 mg CS-3150 (Treatment Sequence 2)
Participants will receive the following treatment sequence (1 treatment per Period): a single oral 40-mg dose of CS-3150, placebo, a 10-mg dose of CS-3150, followed by a 400-mg dose of moxifloxacin.
 Drug: CS-3150
Single, oral administration; 10-mg or 40-mg dose
Other Name: Esaxerenone

Drug: Moxifloxacin
Single, oral administration; 400 mg-tablet
Other Name: Avelox

Drug: Placebo matching moxifloxacin tablet
Placebo tablets matching moxifloxacin tablets
Other Name: Placebo
Experimental: Moxifloxacin (Treatment Sequence 3)
Participants will receive the following treatment sequence (1 treatment per Period): a single oral 400-mg dose of moxifloxacin, 10-mg dose of CS-3150, placebo, 40-mg dose of CS-3150.
 Drug: CS-3150
Single, oral administration; 10-mg or 40-mg dose
Other Name: Esaxerenone

Drug: Moxifloxacin
Single, oral administration; 400 mg-tablet
Other Name: Avelox

Drug: Placebo matching CS-3150
Placebo tablets matching CS-3150 tablets
Other Name: Placebo
Experimental: Placebo (Treatment Sequence 4)
Participants will receive the following treatment sequence (1 treatment per Period): a single oral dose of placebo, 400-mg dose of moxifloxacin, 40-mg dose CS-3150, 10-mg dose of CS-3150.
 Drug: CS-3150
Single, oral administration; 10-mg or 40-mg dose
Other Name: Esaxerenone

Drug: Moxifloxacin
Single, oral administration; 400 mg-tablet
Other Name: Avelox

Drug: Placebo matching moxifloxacin tablet
Placebo tablets matching moxifloxacin tablets
Other Name: Placebo

Drug: Placebo matching CS-3150
Placebo tablets matching CS-3150 tablets
Other Name: Placebo
Outcome Measures
Primary Outcome Measures :
  1. Change in corrected QT (QTc) interval from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, the estimated difference in least square means will be reported between each CS-3150 dose level and placebo in QTc change from baseline.


Secondary Outcome Measures :
  1. Percentage of participants reporting treatment-emergent adverse events (TEAEs) following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
  2. Change in corrected QT (QTc) interval from baseline following oral administration of 1 of 4 treatment sequences with moxifloxacin [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, the estimated difference in least square means will be reported between moxifloxacin and placebo in QTc change from baseline.

  3. Change in the interval between the P and R waves (PR) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, the interval between the P and R waves (PR) at baseline and change from baseline will be summarized by treatment.

  4. Change in QRS wave complex (QRS) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, QRS wave complex (QRS) at baseline and change from baseline will be summarized by treatment.

  5. Change in QT interval (QT) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, QT interval (QT) at baseline and change from baseline will be summarized by treatment.

  6. Change in QTc corrected by Bazett's formula (QTcB) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, QTc corrected by Bazett's formula (QTcB) at baseline and change from baseline will be summarized by treatment.

  7. Change in QTc corrected by Fridericia's formula (QTcF) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, QTc corrected by Fridericia's formula ([QTcF]) at baseline and change from baseline will be summarized by treatment.

  8. Change in heart rate (HR) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    Based on the electrocardiogram tracing, heart rate (HR) at baseline and change from baseline will be summarized by treatment.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy males and/or females 18 years to 45 years of age with a body mass index of 19 kg/m2 to 32 kg/m2 (inclusive)
  • Laboratory results (serum chemistry, hematology, and urinalysis [UA]), liver function, and serum K+ levels within normal range
  • Written informed consent
  • Female participants: Negative pregnancy test and must either be surgically sterile, postmenopausal, or agree to use acceptable nonhormonal contraception.

Exclusion Criteria:

  • All prescription or over-the-counter (OTC) medication (systemic and topical) and herbal supplements will not be permitted for 14 days before the first dose and for the duration of the study.
  • Oral, injected, or implanted hormonal contraception methods, or hormonal replacement therapy, should not have been received in the 3 months prior to the first dose, and for the duration of the study.
  • Female participants: positive pregnancy test or are breast feeding.
  • Supine systolic/diastolic blood pressure at screening, after resting for 10 min, higher than 140/90 mmHg or lower than 90/50 mmHg, confirmed after repeated testing at least approximately 1 h apart.
  • Supine pulse at screening, after resting for 10 min, outside the range of 40 to 100 beats per minute (bpm).
  • QTcF interval duration > 450 ms for male and female obtained as an average from the triplicate screening ECGs after at least 10 min in a fully supine quiet rest.
  • Abnormal waveform morphology on any of the screening ECGs that would preclude accurate measurement of the QT interval duration.
  • Family history of congenital Long QT syndrome (LQTS), a history of surviving an unexplained drowning episode, a history of any form of syncope or loss of consciousness, or known symptomatic cardiac arrhythmias.
  • Known allergy to moxifloxacin.
  • An estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation lower than 90 mL/min.
  • Previous participation in a CS-3150 study within 6 months prior to the single dose of CS-3150.
  • History or current evidence of clinically significant cardiac, hepatic, renal, pulmonary, endocrine, neurologic, infectious, gastrointestinal, hematologic, or oncologic disease as determined by the PI after reviewing screening history, physical examination, laboratory test results, and 12-lead ECG
  • Clinically significant illness (at the discretion of principal investigator) within 4 weeks of first dose, are carriers of Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV), or human immunodeficiency virus (HIV) antibody, and any other reason not deemed suitable for the study (at the discretion of the principal investigator).
Contacts and Locations

Locations
Layout table for location information
United States, Texas
Worldwide Clinical Trials
San Antonio, Texas, United States, 78217
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
Layout table for investigator information
Study Director: Clinical Study Leader Daiichi Sankyo, Inc.
Tracking Information
First Submitted Date  ICMJE July 9, 2019
First Posted Date  ICMJE July 15, 2019
Last Update Posted Date July 15, 2019
Actual Study Start Date  ICMJE November 19, 2015
Actual Primary Completion Date December 23, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 12, 2019) 		Change in corrected QT (QTc) interval from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
On the electrocardiogram tracing, the estimated difference in least square means will be reported between each CS-3150 dose level and placebo in QTc change from baseline.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2019)
  • Percentage of participants reporting treatment-emergent adverse events (TEAEs) following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
  • Change in corrected QT (QTc) interval from baseline following oral administration of 1 of 4 treatment sequences with moxifloxacin [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, the estimated difference in least square means will be reported between moxifloxacin and placebo in QTc change from baseline.
  • Change in the interval between the P and R waves (PR) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, the interval between the P and R waves (PR) at baseline and change from baseline will be summarized by treatment.
  • Change in QRS wave complex (QRS) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, QRS wave complex (QRS) at baseline and change from baseline will be summarized by treatment.
  • Change in QT interval (QT) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, QT interval (QT) at baseline and change from baseline will be summarized by treatment.
  • Change in QTc corrected by Bazett's formula (QTcB) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, QTc corrected by Bazett's formula (QTcB) at baseline and change from baseline will be summarized by treatment.
  • Change in QTc corrected by Fridericia's formula (QTcF) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    On the electrocardiogram tracing, QTc corrected by Fridericia's formula ([QTcF]) at baseline and change from baseline will be summarized by treatment.
  • Change in heart rate (HR) from baseline following oral administration of 1 of 4 treatment sequences with CS-3150 [ Time Frame: Day -1 of Period 1 through Day 8 of Period 4 (~36 days) ]
    Based on the electrocardiogram tracing, heart rate (HR) at baseline and change from baseline will be summarized by treatment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of CS-3150 Exposure on Corrected QT (QTc) Interval Duration in Healthy Volunteers
Official Title  ICMJE A Randomized, Double-Blind, Single-Dose, Placebo- and Positive-Controlled Crossover Study to Evaluate the Effect of Therapeutic and Supratherapeutic Exposure to CS-3150 on QTc Interval Duration in Healthy Male and Female Subjects
Brief Summary This study will test if a study drug (CS-3150) will affect the heart rate in healthy males and females. Two doses of the study drug will be tested. Heart rate is not expected to be different between the study groups.
Detailed Description This study will assess the effect of therapeutic and supratherapeutic plasma exposures of CS-3150 on the corrected QT (QTc) interval duration after administration of single oral 10-mg and 40-mg doses of CS-3150 in healthy male and female participants. This study will also determine the safety and tolerability of CS-3150 administration, assess the effect on electrocardiogram (ECG) parameters, detect QT interval (QT)/QTc prolongation with a positive control (moxifloxacin), characterize pharmacokinetics (PK) of CS-3150, and assess exposure-response relationship of CS-3150 on QTc.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

This is a phase 1, single center, randomized, single-dose, double-blind, double-dummy, placebo- and positive-controlled, 4-period crossover study. Participants will be randomized to one of the following 4 treatment sequences:

  1. CS-3150 (10-mg dose)/CS-3150 (40-mg dose)/moxifloxacin/placebo
  2. CS-3150 (40-mg dose)/placebo/CS-3150 (10-mg dose)/moxifloxacin
  3. Moxifloxacin/CS-3150 (10-mg dose)/placebo/CS-3150 (40-mg dose)
  4. Placebo/moxifloxacin/CS-3150 (40-mg dose)/CS-3150 (10-mg dose)
Masking: Double (Participant, Investigator)
Masking Description:
The Investigator, participants, and all other clinical management and personnel will be blinded to treatment. CS-3150 and moxifloxacin (positive control) treatments will be blinded by matching placebos.
Primary Purpose: Prevention
Condition  ICMJE
  • Hypertension
  • Mineralocorticoid Receptor Antagonist
Intervention  ICMJE
  • Drug: CS-3150
    Single, oral administration; 10-mg or 40-mg dose
    Other Name: Esaxerenone
  • Drug: Moxifloxacin
    Single, oral administration; 400 mg-tablet
    Other Name: Avelox
  • Drug: Placebo matching moxifloxacin tablet
    Placebo tablets matching moxifloxacin tablets
    Other Name: Placebo
  • Drug: Placebo matching CS-3150
    Placebo tablets matching CS-3150 tablets
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: 10 mg CS-3150 (Treatment Sequence 1)
    Participants will receive the following treatment sequence (1 treatment per Period): a single oral 10-mg dose of CS-3150, a 40-mg dose of CS-3150, a 400-mg dose of moxifloxacin, followed by placebo.
    Interventions:
    • Drug: CS-3150
    • Drug: Moxifloxacin
    • Drug: Placebo matching moxifloxacin tablet
  • Experimental: 40 mg CS-3150 (Treatment Sequence 2)
    Participants will receive the following treatment sequence (1 treatment per Period): a single oral 40-mg dose of CS-3150, placebo, a 10-mg dose of CS-3150, followed by a 400-mg dose of moxifloxacin.
    Interventions:
    • Drug: CS-3150
    • Drug: Moxifloxacin
    • Drug: Placebo matching moxifloxacin tablet
  • Experimental: Moxifloxacin (Treatment Sequence 3)
    Participants will receive the following treatment sequence (1 treatment per Period): a single oral 400-mg dose of moxifloxacin, 10-mg dose of CS-3150, placebo, 40-mg dose of CS-3150.
    Interventions:
    • Drug: CS-3150
    • Drug: Moxifloxacin
    • Drug: Placebo matching CS-3150
  • Experimental: Placebo (Treatment Sequence 4)
    Participants will receive the following treatment sequence (1 treatment per Period): a single oral dose of placebo, 400-mg dose of moxifloxacin, 40-mg dose CS-3150, 10-mg dose of CS-3150.
    Interventions:
    • Drug: CS-3150
    • Drug: Moxifloxacin
    • Drug: Placebo matching moxifloxacin tablet
    • Drug: Placebo matching CS-3150
Publications * Mendell J, Kobayashi F, Shimizu T. Randomized, Double-Blind, Single-Dose, Placebo-Controlled Crossover Study to Evaluate the Effects of Esaxerenone on QTc Interval in Healthy Subjects. Clin Pharmacol Drug Dev. 2020 Aug;9(6):709-718. doi: 10.1002/cpdd.794. Epub 2020 Apr 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 12, 2019) 		55
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 23, 2015
Actual Primary Completion Date December 23, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy males and/or females 18 years to 45 years of age with a body mass index of 19 kg/m2 to 32 kg/m2 (inclusive)
  • Laboratory results (serum chemistry, hematology, and urinalysis [UA]), liver function, and serum K+ levels within normal range
  • Written informed consent
  • Female participants: Negative pregnancy test and must either be surgically sterile, postmenopausal, or agree to use acceptable nonhormonal contraception.

Exclusion Criteria:

  • All prescription or over-the-counter (OTC) medication (systemic and topical) and herbal supplements will not be permitted for 14 days before the first dose and for the duration of the study.
  • Oral, injected, or implanted hormonal contraception methods, or hormonal replacement therapy, should not have been received in the 3 months prior to the first dose, and for the duration of the study.
  • Female participants: positive pregnancy test or are breast feeding.
  • Supine systolic/diastolic blood pressure at screening, after resting for 10 min, higher than 140/90 mmHg or lower than 90/50 mmHg, confirmed after repeated testing at least approximately 1 h apart.
  • Supine pulse at screening, after resting for 10 min, outside the range of 40 to 100 beats per minute (bpm).
  • QTcF interval duration > 450 ms for male and female obtained as an average from the triplicate screening ECGs after at least 10 min in a fully supine quiet rest.
  • Abnormal waveform morphology on any of the screening ECGs that would preclude accurate measurement of the QT interval duration.
  • Family history of congenital Long QT syndrome (LQTS), a history of surviving an unexplained drowning episode, a history of any form of syncope or loss of consciousness, or known symptomatic cardiac arrhythmias.
  • Known allergy to moxifloxacin.
  • An estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation lower than 90 mL/min.
  • Previous participation in a CS-3150 study within 6 months prior to the single dose of CS-3150.
  • History or current evidence of clinically significant cardiac, hepatic, renal, pulmonary, endocrine, neurologic, infectious, gastrointestinal, hematologic, or oncologic disease as determined by the PI after reviewing screening history, physical examination, laboratory test results, and 12-lead ECG
  • Clinically significant illness (at the discretion of principal investigator) within 4 weeks of first dose, are carriers of Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV), or human immunodeficiency virus (HIV) antibody, and any other reason not deemed suitable for the study (at the discretion of the principal investigator).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04019652
Other Study ID Numbers  ICMJE CS3150-A-U106
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Study Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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