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NCT01227265

Placebo Controlled Study of Preladenant in Participants With Moderate to Severe Parkinson's Disease (P07037)

Completed Phase 3 Results posted Last updated 24 September 2018
What this trial tests

Phase 3 trial testing Preladenant in Parkinson Disease in 476 participants. Completed in 16 April 2013.

Timeline
19 November 2010
Primary endpoint
4 April 2013
16 April 2013

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment476
Start date19 November 2010
Primary completion4 April 2013
Estimated completion16 April 2013

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 30 to 85, any sex, with Parkinson Disease or Idiopathic Parkinson Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Average "Off" Time (Hours Per Day) at Week 12 Primary · Baseline and Week 12

The "on" state is defined as the period of time during which a patient's symptoms of PD improve or disappear following treatment with 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"

GroupValue95% CI
Preladenant 2 mg-1.0± 0.20
Preladenant 5 mg-1.1± 0.20
Placebo-0.8± 0.19
Percentage of Participants With >30% Change (Reduction) From Baseline at Week 12 in Mean "Off" Time Secondary · Baseline and Week 12

A participant with at least a 30% reduction in mean "off" time from Baseline to End of Treatment (Week 12) is considered as "responder". The "on" state is defined as the period of time during which a patient's symptoms of PD improve or disappear following treatment with 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

GroupValue95% CI
Preladenant 2 mg37.1
Preladenant 5 mg36.9
Placebo30.5
Change From Baseline in Average "On" Time (Hours Per Day) Without Troublesome Dyskinesia at Week 12 Secondary · Baseline and Week 12

"On" time is when a PD participant's symptoms are improved. Mean "on" time without troublesome dyskinesias is derived from the available diary data collected for 3 days immediately prior to a clinic visit. "On" time without troublesome dyskinesia is the sum of "on" time without dyskinesia plus "on" time with non-troublesome dyskinesia as recorded in the diary. The mean change from baseline in "on" time was based on a cLDA with treatment, time, and treatment-by-time interaction as fixed effects and subject as random effect.

GroupValue95% CI
Preladenant 2 mg0.6± 0.21
Preladenant 5 mg0.7± 0.21
Placebo0.5± 0.20
Number of Participants With Systolic Blood Pressure (SBP) ≥180 mmHg and 20 mmHg Increase Primary · Up to Week 14

The number of participants with Systolic Blood Pressure (SBP) ≥180 mmHg and 20 mmHg increase was reported. Participants lie supine at rest for 5 minutes, then have a single BP measurement taken (ie, 1 reading). Participants then stand for 3 minutes at rest, followed by a single BP measurement (1 reading) in the standing position.

Supine
GroupValue95% CI
Preladenant 2 mg0
Preladenant 5 mg1
Placebo0
Standing
GroupValue95% CI
Preladenant 2 mg1
Preladenant 5 mg0
Placebo0
Number of Participants With Diastolic Blood Pressure (DBP) ≥105 mmHg and 15 mmHg Increase Primary · Up to Week 14

The number of participants with Diastolic Blood Pressure (DBP) ≥105 mmHg and 15 mmHg increase was reported. Participants lie supine at rest for 5 minutes, then have a single BP measurement taken (ie, 1 reading). Participants then stand for 3 minutes at rest, followed by a single BP measurement (1 reading) in the standing position.

Supine
GroupValue95% CI
Preladenant 2 mg1
Preladenant 5 mg2
Placebo3
Standing
GroupValue95% CI
Preladenant 2 mg7
Preladenant 5 mg3
Placebo6
Percentage of Participants With Suicidality Primary · Up to Week 12

The percentage of participants with suicidality using the Columbia - Suicide Severity Rating Scale (C-SSRS) was reported. The C-SSR was used in this study only for the purpose of safety monitoring by measuring the incidence of different types of suicidality categories during treatment. The assessment was done by the nature of the responses, not by a numbered scale. Participants who reported at least one occurrence of suicidal behavior or suicidal ideation were counted as having experienced suicidality. Suicidal behavior included suicide attempt, aborted attempt, interrupted attempt, or prepara

GroupValue95% CI
Preladenant 2 mg3
Preladenant 5 mg4
Placebo1
Change From Baseline in Total Epworth Sleepiness Scale (ESS) at Week 12 Primary · Baseline and Week 12

The ESS is a self-administered questionnaire providing a measure of a person's general level of daytime sleepiness, or their average sleep propensity in daily life. The scale consists of 8 situations in which the participant rates their tendency to become sleepy on a scale of 0=no chance of dozing to 3=high chance of dozing. The overall score is the sum of the scores for the 8 situations for a minimum of 0 and a maximum of 24 with a higher score indicating greater sleepiness. The mean change from baseline in total EES was based on a cLDA with treatment, time, and treatment-by-time interaction

GroupValue95% CI
Preladenant 2 mg-0.4± 0.28
Preladenant 5 mg-0.0± 0.29
Placebo-0.2± 0.28

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 14 weeks (including 14 days of follow-up). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Preladenant 2 mg
Serious: 5/157 (3%)
Deaths:
Preladenant 5 mg
Serious: 2/157 (1%)
Deaths:
Placebo
Serious: 4/159 (3%)
Deaths:

Serious adverse events (21 terms)

ReactionSystemPreladenant 2 mgPreladenant 5 mgPlacebo
AnaemiaBlood and lymphatic system disorders
DiverticulumGastrointestinal disorders
DysphagiaGastrointestinal disorders
HaemorrhoidsGastrointestinal disorders
Lower Gastrointestinal HaemorrhageGastrointestinal disorders
Chest PainGeneral disorders
LymphangitisInfections and infestations
PneumoniaInfections and infestations
ContusionInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Kidney RuptureInjury, poisoning and procedural complications
Subdural HaematomaInjury, poisoning and procedural complications
Upper Limb FractureInjury, poisoning and procedural complications
Wrist FractureInjury, poisoning and procedural complications
HypercalcaemiaMetabolism and nutrition disorders
Cerebral HaematomaNervous system disorders
Completed SuicidePsychiatric disorders
Confusional StatePsychiatric disorders
DepressionPsychiatric disorders
Stress Urinary IncontinenceRenal and urinary disorders
Decubitus UlcerSkin and subcutaneous tissue disorders
Other adverse events (6 terms — click to expand)

ReactionSystemPreladenant 2 mgPreladenant 5 mgPlacebo
ConstipationGastrointestinal disorders
HeadacheNervous system disorders
DyskinesiaNervous system disorders
FallInjury, poisoning and procedural complications
DizzinessNervous system disorders
NauseaGastrointestinal disorders

Most-reported serious reactions: Anaemia, Diverticulum, Dysphagia, Haemorrhoids, Lower Gastrointestinal Haemorrhage, Chest Pain, Lymphangitis, Pneumonia.

Data from ClinicalTrials.gov NCT01227265 adverse events section.

Sponsor's own description

This is a study of the efficacy and safety of preladenant in adult participants with moderate to severe Parkinson's Disease (PD). While on this study, participants will continue to take their usual, prescribed, stable regimen of levodopa (L-dopa) or L-dopa plus adjunct PD medications and will be randomized to receive 2 mg preladenant, 5 mg preladenant, or placebo, twice daily, for 12 weeks. After that, participants may choose to receive additional treatment with preladenant. The primary hypothesis is that at least the 5 mg twice daily dose of preladenant is superior to placebo as measured by the change from Baseline to Week 12 in the mean "off" time.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Adenosine receptors as drug targets--what are the challenges?
    Chen JF, Eltzschig HK, Fredholm BB. · · 2013 · cited 678× · PMID 23535933 · DOI 10.1038/nrd3955
  2. Adenosine A1 and A2A Receptors in the Brain: Current Research and Their Role in Neurodegeneration.
    Stockwell J, Jakova E, Cayabyab FS. · · 2017 · cited 142× · PMID 28441750 · DOI 10.3390/molecules22040676
  3. Preladenant as an Adjunctive Therapy With Levodopa in Parkinson Disease: Two Randomized Clinical Trials and Lessons Learned.
    Hauser RA, Stocchi F, Rascol O, Huyck SB, et al · · 2015 · cited 73× · PMID 26523919 · DOI 10.1001/jamaneurol.2015.2268
  4. Adenosine A(2A) Receptor Antagonists and Parkinson's Disease.
    Shook BC, Jackson PF. · · 2011 · cited 70× · PMID 22860156 · DOI 10.1021/cn2000537
  5. Targeting Adenosine Signaling in Parkinson's Disease: From Pharmacological to Non-pharmacological Approaches.
    Nazario LR, da Silva RS, Bonan CD. · · 2017 · cited 29× · PMID 29217998 · DOI 10.3389/fnins.2017.00658
  6. The Adenosinergic System as a Therapeutic Target in the Vasculature: New Ligands and Challenges.
    Sousa JB, Diniz C. · · 2017 · cited 17× · PMID 28481238 · DOI 10.3390/molecules22050752
  7. Drug Development for Alzheimer's and Parkinson's Disease: Where Do We Go Now?
    Sequeira L, Benfeito S, Fernandes C, Lima I, et al · · 2024 · cited 12× · PMID 38931832 · DOI 10.3390/pharmaceutics16060708
  8. Targeting of G-protein coupled receptors in sepsis.
    Rehman A, Baloch NU, Morrow JP, Pacher P, et al · · 2020 · cited 11× · PMID 32197794 · DOI 10.1016/j.pharmthera.2020.107529

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