Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Dose Finding Study of Preladenant (SCH 420814) for the Treatment of Parkinson's Disease (PD) in Japanese Patients (P06402)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01294800
Recruitment Status : Completed
First Posted : February 14, 2011
Results First Posted : October 11, 2016
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Parkinson's Disease
Interventions Drug: Preladenant
Drug: Placebo tablet to match Preladenant
Enrollment 450
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Hide Arm/Group Description Participants received preladenant 2 mg taken orally twice daily (BID), one tablet in the morning and one tablet in the evening, for 12 weeks. Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Period Title: Overall Study
Started 111 113 113 113
Completed 100 103 96 97
Not Completed 11 10 17 16
Reason Not Completed
Adverse Event             7             6             12             5
Subject Withdrew Consent             2             2             2             11
Lost to Follow-up             0             0             1             0
Non-compliance With Protocol             0             1             1             0
Did Not Meet Protocol Eligibility             2             1             1             0
Arm/Group Title Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo Total
Hide Arm/Group Description Participants received preladenant 2 mg taken orally twice daily (BID), one tablet in the morning and one tablet in the evening, for 12 weeks. Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 111 113 113 113 450
Hide Baseline Analysis Population Description
All Randomized Participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 111 participants 113 participants 113 participants 113 participants 450 participants
68.0  (7.9) 67.6  (8.3) 67.8  (7.6) 65.8  (9.1) 67.3  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 113 participants 113 participants 113 participants 450 participants
Female
54
  48.6%
66
  58.4%
69
  61.1%
64
  56.6%
253
  56.2%
Male
57
  51.4%
47
  41.6%
44
  38.9%
49
  43.4%
197
  43.8%
1.Primary Outcome
Title Change From Baseline in Mean “Off” Time (Hours Per Day) at Week 12
Hide Description The "on" state is defined as the period of time during which a participant's symptoms of PD improve or disappear following treatment with levodopa (L-dopa) or dopamine agonists. The "off" state is defined as the period of time characterized by the return of symptoms (i..e. tremor, slowness, and rigidity) following treatment with L-dopa or dopamine agonists. Study participants reported their symptoms at half-hour intervals as "off", "on", or "asleep" on their daily diary for 3 days before randomization (baseline) and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "off" time was based on a constrained longitudinal data analysis with treatment, time, and treatment-by-time interaction as fixed effects, and an unstructured covariance matrix was used to model the correlation among repeated measurements.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population, which consisted of all randomized participants who received at least one dose of study treatment; had endpoint data subsequent to at least one dose of study treatment; and had baseline data for those analyses requiring baseline data.
Arm/Group Title Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Hide Arm/Group Description:
Participants received preladenant 2 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Overall Number of Participants Analyzed 98 101 93 90
Mean (Standard Deviation)
Unit of Measure: Hours/Day
-1.2  (2.3) -1.0  (2.6) -0.9  (2.2) -0.5  (3.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preladenant 2 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0564
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.37 to 0.02
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Preladenant 5 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1844
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.16 to 0.22
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Preladenant 10 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3386
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.04 to 0.36
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
Time Frame Up to 14 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated population, which included all participants who received at least one dose of study drug
Arm/Group Title Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Hide Arm/Group Description:
Participants received preladenant 2 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Overall Number of Participants Analyzed 111 113 113 113
Measure Type: Number
Unit of Measure: Participants
53 60 69 55
3.Primary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Hide Description An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
Time Frame Up to 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated population, which included all participants who received at least one dose of study drug
Arm/Group Title Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Hide Arm/Group Description:
Participants received preladenant 2 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Overall Number of Participants Analyzed 111 113 113 113
Measure Type: Number
Unit of Measure: Participants
6 6 12 5
4.Secondary Outcome
Title Percentage of Participants With ≥30% Reduction in “Off” Time at Week 12
Hide Description The proportion of responders (≥30% Reduction in “Off” Time at Week 12) was analyzed using a generalized linear mixed model with baseline mean OFF time (hours/day) as a covariate and treatment-by-time interaction as a fixed effect, and an unstructured covariance matrix was used to model the correlation among repeated measurements. Responder rates for each treatment arm are presented as are differences from placebo with 95% confidence interval.
Time Frame Up to 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population, which consisted of all randomized participants who received at least one dose of study treatment; had endpoint data subsequent to at least one dose of study treatment; and had baseline data for those analyses requiring baseline data.
Arm/Group Title Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Hide Arm/Group Description:
Participants received preladenant 2 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Overall Number of Participants Analyzed 110 113 110 112
Measure Type: Number
Unit of Measure: Percentage of participants
34.5 34.6 24.6 28.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preladenant 2 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.404
Comments [Not Specified]
Method A generalized linear mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions of responders
Estimated Value 5.7
Confidence Interval (2-Sided) 95%
-7.75 to 19.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Preladenant 5 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.390
Comments [Not Specified]
Method A generalized linear mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions of responders
Estimated Value 5.7
Confidence Interval (2-Sided) 95%
-7.73 to 18.81
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Preladenant 10 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.508
Comments [Not Specified]
Method A generalized linear mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions of responders
Estimated Value -4.9
Confidence Interval (2-Sided) 95%
-17.78 to 7.97
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Mean “On” Time Without Troublesome Dyskinesias (Hours Per Day) at Week 12
Hide Description When a participant is "on" without dyskinesias, parkinsonian symptoms have dissipated and the participant is experiencing no uncontrollable extraneous movements. Study participants reported their parkinsonian symptoms at half-hour intervals as "off", "on without dyskinesia", "on with non-troublesome dyskinesia", "on with troublesome dyskinesia", or "asleep" on their daily diary for 3 days before randomization and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "on without troublesome dyskinesia" time was based on a constrained longitudinal data analysis with treatment, time, and treatment-by-time interaction as fixed effects, and an unstructured covariance matrix was used to model the correlation among repeated measurements.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population, which consisted of all randomized participants who received at least one dose of study treatment; had endpoint data subsequent to at least one dose of study treatment; and had baseline data for those analyses requiring baseline data.
Arm/Group Title Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Hide Arm/Group Description:
Participants received preladenant 2 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Overall Number of Participants Analyzed 98 101 93 90
Mean (Standard Deviation)
Unit of Measure: Hours/Day
1.3  (2.5) 1.0  (2.9) 1.0  (2.4) 0.5  (2.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preladenant 2 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0509
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.00 to 1.43
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Preladenant 5 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1847
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-0.23 to 1.19
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Preladenant 10 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2021
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-0.25 to 1.19
Estimation Comments [Not Specified]
Time Frame Up to 14 weeks
Adverse Event Reporting Description All Participants as Treated population, which included all participants who received at least one dose of study drug
 
Arm/Group Title Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Hide Arm/Group Description Participants received preladenant 2 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
All-Cause Mortality
Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/111 (8.11%)      5/113 (4.42%)      7/113 (6.19%)      3/113 (2.65%)    
Blood and lymphatic system disorders         
ANAEMIA  1  0/111 (0.00%)  0 0/113 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0
Gastrointestinal disorders         
INGUINAL HERNIA  1  1/111 (0.90%)  1 0/113 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0
LARGE INTESTINE POLYP  1  0/111 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0
LOWER GASTROINTESTINAL HAEMORRHAGE  1  1/111 (0.90%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0 0/113 (0.00%)  0
General disorders         
GAIT DISTURBANCE  1  0/111 (0.00%)  0 0/113 (0.00%)  0 1/113 (0.88%)  1 1/113 (0.88%)  1
Hepatobiliary disorders         
DRUG-INDUCED LIVER INJURY  1  0/111 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0
Infections and infestations         
CELLULITIS  1  0/111 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0
PNEUMONIA  1  1/111 (0.90%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0 0/113 (0.00%)  0
Injury, poisoning and procedural complications         
FEMUR FRACTURE  1  0/111 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0
HEAT STROKE  1  1/111 (0.90%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0 0/113 (0.00%)  0
SPINAL COMPRESSION FRACTURE  1  1/111 (0.90%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0 0/113 (0.00%)  0
ULNA FRACTURE  1  0/111 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0
Musculoskeletal and connective tissue disorders         
JAW CYST  1  1/111 (0.90%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0 0/113 (0.00%)  0
PAIN IN EXTREMITY  1  0/111 (0.00%)  0 0/113 (0.00%)  0 0/113 (0.00%)  0 1/113 (0.88%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
COLON CANCER  1  0/111 (0.00%)  0 0/113 (0.00%)  0 2/113 (1.77%)  2 0/113 (0.00%)  0
METASTASES TO LYMPH NODES  1  0/111 (0.00%)  0 0/113 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0
Nervous system disorders         
PARKINSON'S DISEASE  1  2/111 (1.80%)  2 0/113 (0.00%)  0 2/113 (1.77%)  2 0/113 (0.00%)  0
Psychiatric disorders         
IMPULSE-CONTROL DISORDER  1  0/111 (0.00%)  0 0/113 (0.00%)  0 0/113 (0.00%)  0 1/113 (0.88%)  1
Renal and urinary disorders         
CYSTITIS HAEMORRHAGIC  1  0/111 (0.00%)  0 0/113 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0
URINARY RETENTION  1  1/111 (0.90%)  1 0/113 (0.00%)  0 0/113 (0.00%)  0 0/113 (0.00%)  0
Social circumstances         
ACTIVITIES OF DAILY LIVING IMPAIRED  1  0/111 (0.00%)  0 0/113 (0.00%)  0 1/113 (0.88%)  1 0/113 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Preladenant 2 mg Preladenant 5 mg Preladenant 10 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/111 (17.12%)      23/113 (20.35%)      25/113 (22.12%)      14/113 (12.39%)    
Gastrointestinal disorders         
CONSTIPATION  1  3/111 (2.70%)  3 5/113 (4.42%)  5 8/113 (7.08%)  8 4/113 (3.54%)  4
Infections and infestations         
NASOPHARYNGITIS  1  5/111 (4.50%)  5 9/113 (7.96%)  11 8/113 (7.08%)  8 8/113 (7.08%)  10
Injury, poisoning and procedural complications         
FALL  1  8/111 (7.21%)  10 3/113 (2.65%)  3 7/113 (6.19%)  8 0/113 (0.00%)  0
Nervous system disorders         
DYSKINESIA  1  3/111 (2.70%)  3 7/113 (6.19%)  7 7/113 (6.19%)  7 2/113 (1.77%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
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 investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including, without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media, eg, any computer access system such as the Internet, World Wide Web, etc) that report any results of the trial.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01294800     History of Changes
Other Study ID Numbers: P06402
MK-3814-026 ( Other Identifier: Merck )
First Submitted: February 10, 2011
First Posted: February 14, 2011
Results First Submitted: August 18, 2016
Results First Posted: October 11, 2016
Last Update Posted: November 8, 2018