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Safety and Tolerability of MK-5478 in Participants With Hypertension (5478-001)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01025843
First received: December 2, 2009
Last updated: January 28, 2016
Last verified: January 2016
Results First Received: January 28, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Hypertension
Interventions: Drug: MK-5478
Drug: Comparator: Candesartan cilexetil
Drug: Comparator: Pbo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A Part II of this study was planned. However, since the efficacy criteria for advancing to Part II were not met in Part I, this study was considered completed with the completion of Part I. Therefore participants were not recruited for Part II.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Pbo → 5 mg → Candesartan → 24 mg → 38 mg Placebo in Period 1; 5 mg MK-5478 in Period 2; Candesartan in Period 3; 24 mg MK-5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
1 mg → 5 mg → 12 mg → Candesartan → Pbo 1 mg MK-5478 in Period 1; 5 mg MK-5478 in Period 2; 12 mg MK-5478 in Period 3; Candesartan in Period 4; and Placebo in Period 5. There was a minimum 7 days washout between periods.
1 mg → Candesartan → Pbo → 24 mg → 38 mg 1 mg MK-5478 in Period 1; Candesartan in Period 2: Placebo in Period 3; 24 mg MK- 5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
1 mg → 5 mg → 12 mg → Pbo → Candesartan 1 mg MK-5478 in Period 1; 5 mg MK-5478 in Period 2; 12 mg MK-5478 in Period 3; Placebo in Period 4; and Candesartan in Period 5. There was a minimum 7 days washout between periods.
Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan Placebo in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and Candesartan in Period 5. There was a minimum 7 days washout between periods.
2 mg→Pbo → Candesartan → Pbo Fed → 38 mg 2 mg MK-5478 in Period 1; Placebo in Period 2; Candesartan in Period 3; Placebo in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg 2 mg MK-5478 in Period 1; Candesartan in Period 2; Placebo in Period 3; Candesartan in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo 2 mg MK-5478 in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and Placebo in Period 5. There was a minimum 7 days washout between periods.
Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg Candesartan in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
Candesartan → Pbo → 12 mg → 24 mg → 38 mg Candesartan in Period 1; Placebo in Period 2; 12 mg MK-5478 in Period 3; 24 mg MK- 5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods

Participant Flow for 9 periods

Period 1:   Period 1
    Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg
STARTED   2   2   2   2   2   2   2   2   2   2 
COMPLETED   2   2   2   2   2   2   2   2   2   2 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0 

Period 2:   Washout 1
    Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg
STARTED   2   2   2   2   2   2   2   2   2   2 
COMPLETED   2   2   2   2   2   2   2   2   2   2 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0 

Period 3:   Period 2
    Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg
STARTED   2   2   2   2   2   2   2   2   2   2 
COMPLETED   2   2   2   2   2   2   2   2   2   2 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0 

Period 4:   Washout 2
    Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg
STARTED   2   2   2   2   2   2   2   2   2   2 
COMPLETED   2   2   2   2   2   2   2   2   2   2 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0 

Period 5:   Period 3
    Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg
STARTED   2   2   2   2   2   2   2   2   2   2 
COMPLETED   2   2   2   2   2   2   2   2   2   2 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0 

Period 6:   Washout 3
    Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg
STARTED   2   2   2   2   2   2   2   2   2   2 
COMPLETED   2   2   2   2   2   2   2   2   2   2 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0 

Period 7:   Period 4
    Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg
STARTED   2   2   2   2   2   2   2   2   2   2 
COMPLETED   2   2   2   2   2   2   2   2   2   2 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0 

Period 8:   Washout 4
    Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg
STARTED   2   2   2   2   2   2   2   2   2   2 
COMPLETED   2   2   1   1   2   2   2   2   2   2 
NOT COMPLETED   0   0   1   1   0   0   0   0   0   0 
Withdrawal by Subject                0                0                1                1                0                0                0                0                0                0 

Period 9:   Period 5
    Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg
STARTED   2   2   1   1   2   2   2   2   2   2 
COMPLETED   2   2   1   1   2   2   2   2   2   2 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants

Reporting Groups
  Description
Pbo → 5 mg → Candesartan → 24 mg → 38 mg Placebo in Period 1; 5 mg MK-5478 in Period 2; Candesartan in Period 3; 24 mg MK-5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods
1 mg → 5 mg → 12 mg → Candesartan → Pbo 1 mg MK-5478 in Period 1; 5 mg MK-5478 in Period 2; 12 mg MK-5478 in Period 3; Candesartan in Period 4; and Placebo in Period 5. There was a minimum 7 days washout between periods.
1 mg → Candesartan → Pbo → 24 mg → 38 mg 1 mg MK-5478 in Period 1; Candesartan in Period 2: Placebo in Period 3; 24 mg MK- 5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
1 mg → 5 mg → 12 mg → Pbo → Candesartan 1 mg MK-5478 in Period 1; 5 mg MK-5478 in Period 2; 12 mg MK-5478 in Period 3; Placebo in Period 4; and Candesartan in Period 5. There was a minimum 7 days washout between periods.
Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan Placebo in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and Candesartan in Period 5. There was a minimum 7 days washout between periods.
2 mg→Pbo → Candesartan → Pbo Fed → 38 mg 2 mg MK-5478 in Period 1; Placebo in Period 2; Candesartan in Period 3; Placebo in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg 2 mg MK-5478 in Period 1; Candesartan in Period 2; Placebo in Period 3; Candesartan in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo 2 mg MK-5478 in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and Placebo in Period 5. There was a minimum 7 days washout between periods.
Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg Candesartan in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.
Candesartan → Pbo → 12 mg → 24 mg → 38 mg Candesartan in Period 1; Placebo in Period 2; 12 mg MK-5478 in Period 3; 24 mg MK- 5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods
Total Total of all reporting groups

Baseline Measures
   Pbo → 5 mg → Candesartan → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Candesartan → Pbo   1 mg → Candesartan → Pbo → 24 mg → 38 mg   1 mg → 5 mg → 12 mg → Pbo → Candesartan   Pbo → 8 mg→ 18 mg → 2 mg Fed → Candesartan   2 mg→Pbo → Candesartan → Pbo Fed → 38 mg   2 mg→Candesartan→ Pbo → Candesartan Fed → 38 mg   2 mg → 8 mg → 18 mg → 2 mg Fed → Pbo   Candesartan→8 mg→ 18 mg → 2 mg Fed → 38 mg   Candesartan → Pbo → 12 mg → 24 mg → 38 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 2   2   2   2   2   2   2   2   2   2   20 
Age 
[Units: Years]
Median (Full Range)
 46.5 
 (46 to 47) 
 38.5 
 (29 to 48) 
 46.0 
 (45 to 47) 
 35.0 
 (21 to 49) 
 37.5 
 (36 to 39) 
 44.5 
 (40 to 49) 
 48.0 
 (46 to 50) 
 46.5 
 (44 to 49) 
 45.0 
 (42 to 48) 
 39.0 
 (38 to 40) 
 45.5 
 (21 to 50) 
Gender 
[Units: Participants]
                     
Female   0   0   0   0   0   0   0   0   0   0   0 
Male   2   2   2   2   2   2   2   2   2   2   20 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With One or More Adverse Events (AEs)   [ Time Frame: Up to 14 days after administration of last dose of study drug (up to Day 52) ]

2.  Primary:   Number of Participants Who Discontinued Treatment Due to an AE   [ Time Frame: Up to 24 hours after administration of study drug ]

3.  Secondary:   Area Under the Plasma Concentration Versus Time Curve (AUC 0-infinity) of MK-5478 and Candesartan   [ Time Frame: Pre-dose and up to 48 hours postdose ]

4.  Secondary:   Change From Baseline in Aortic Augmentation Index (AIx) of MK-5478 and Candesartan   [ Time Frame: Baseline and 1 to 3 hours postdose ]

5.  Secondary:   Maximum Plasma Concentration (Cmax) of MK-5478 and Candesartan   [ Time Frame: Pre-dose and up to 48 hours postdose ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com



Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01025843     History of Changes
Other Study ID Numbers: 5478-001
2009-016048-38 ( EudraCT Number )
Study First Received: December 2, 2009
Results First Received: January 28, 2016
Last Updated: January 28, 2016
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP