Clinical trial NCT02337764: A Long-term, Phase 3 Study of TVP-1012 (1 mg) in Levodopa Treated Parkinson's Disease Participants
Official title: A Multicenter, Open-label, Long-term, Phase 3 Study to Evaluate the Safety and Efficacy of TVP-1012 at 1 mg in Levodopa Treated Parkinson's Disease Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-01-14
Enrollment: 222
Sex: ALL
Minimum age (years): 30
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate long-term safety of TVP-1012 (1 mg/day) with levodopa in Japanese participants with Parkinson's disease.

Detailed description: This is a multicenter, open-label, long-term, phase 3 study to evaluate the safety and efficacy of long-term administration of TVP-1012 at 1 mg with levodopa in Japanese participants with Parkinson's disease.

The study period consisted of a 2-week run-in period and a subsequent 52-week treatment period. Participants fulfilling the inclusion criteria and did not meet any of the exclusion criteria at the start of the run-in period (Week -2) and also at the end of the run-in period (Week 0) were enrolled in the study, and received 1 mg of TVP-1012 once daily for 52 weeks, in an unblinded manner, from the day after Week 0.

Eligibility criteria: Inclusion Criteria:

* In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements.
* The participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
* The participant has a diagnosis of Parkinson's disease according to the diagnostic criteria of the UK Parkinson's Disease Society Brain Bank.
* The participant has received a levodopa combination drug for \>= 1 month at the start of the run-in period and has either of the following.

  * Wearing off phenomenon
  * Decreased response to levodopa combination drugs
* The participant has been receiving a levodopa combination drug a stable dose regimen since the start of the run-in period.
* The participant is an outpatient of either sex aged \>= 30 and \< 80 years at the time of consent.
* A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent to 1 month after the last dose of the investigational drug.

Exclusion Criteria:

* The participant has received any investigational medication within 90 days prior to the start of the run-in period.
* The participant has received TVP-1012 in the past.
* The participant is a study site employee, an immediate family member, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
* Participant has donated 400 mL or more of his or her blood volume within 90 days prior to the start of the run-in period.
* The participant has Modified Hoehn \& Yahr stage 5 (or stage 5 at eather on-time or off-time for the participant with wearing off phenomenon) at the start of the run-in period.
* The participant has severe dyskinesia.
* The participant has unstable systemic disease.
* The participant has a Mini-Mental State Examinations (MMSE) score of \<= 24 at the start of the run-in period..
* The participant has known or a history of schizophrenia, major or severe depression, or any other clinically significant psychiatric disease.
* The participant has a history of hypersensitivity or allergies to TVP-1012 (including any associated excipients) or selegiline.
* The participant has a history of clinically significant hypertension or other reactions associated with ingestion of tyramine-rich food (e.g., cheese, lever, herring, yeast, horsebean, banana, beer or wine).
* The participant has a history or concurrent of drug abuse or alcohol dependence.
* The participant has received neurosurgical intervention for Parkinson's disease (e.g., pallidotomy, thalamotomy, deep brain stimulation).
* The participant has received transcranial magnetic stimulation within 6 months prior to the start of the run-in period.
* The participant has received selegiline, pethidine, tramadol, reserpine or methyldopa within 90 days prior to the start of the run-in period.
* The participant has received single agent of levodopa, any psychoneurotic agent or antiemetic medication of dopamine agonist within 14 days prior to the start of the run-in period. However, the participant has been receiving quetiapine or domperidone with a stable dose regimen for \>= 14 days prior to the start of the run-in period may be included in the study.
* The participant is required to take any of the prohibited concomitant medications or treatments.
* If female, the participant is pregnant or lactating or intending to become pregnant during, or within 1 month after the last administration of study medication in this study; or intending to donate ova during such time period.
* The participant has clinically significant neurologic, cardiovascular, pulmonary, hepatic (including mild cirrhosis), renal, metabolic, gastrointestinal, urological, endocrine, or hematological disease.
* The participant has clinically significant or unstable brain or cardiovascular disease, such as:

  * clinically significant arrhythmia or cardiac valvulopathy,
  * heart failure of NYHA Class II or higher,
  * concurrent or a history of ischemic cardiac disease within 6 months prior to the start of the run-in period,
  * concurrent or a history of clinically significant cerebrovascular disease within 6 months prior to the stat of the run-in period,
  * severe hypertension (systolic blood pressure of 180 mmHg or higher, or diastolic blood pressure of 110 mmHg or higher),
  * clinically significant orthostatic hypotension (including those with diastolic pressure decrease of 30 mmHg or more following postural change from supine/sitting position to standing position), or
  * a history of syncope due to hypotension within 2 years prior to the stat of the run-in period.
* The participant is required surgery or hospitalization for surgery during the study period.
* Participant has a history of cancer within 5 years prior to the start of the run-in period, except cervix carcinoma in situ which has completely cured.
* The participant has acquired immunodeficiency syndrome (AIDS) \[including human immunodeficiency virus (HIV) carrier\], or hepatitis \[including viral hepatitis carrier such as hepatitis B surface (HBs) antigen or hepatitis C antibody (HCV) positive\]. However, the participant who has a negative result for HCV antigen or HCV-RNA can be included in the study.
* The participant with laboratory data meeting any of the following at the start of the run-in period:

  * Creatinine \>= 2 x upper limit of normal (ULN)
  * Total bilirubin \>= 2 x ULN
  * ALT or AST \>= 1.5 x ULN
  * ALP \>= 3 x ULN
* The participant has received any of the prohibited concomitant medications or treatments during the run-in period
* The participant who, in the opinion of the investigator or sub-investigator, is unsuitable for any other reason.

Primary outcomes:
measure: Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 52
Secondary outcomes:
measure: Number of Participants With TEAE Related to Clinical Laboratory Tests
timeFrame: Up to Week 52
measure: Number of Participants With Markedly Abnormal Vital Signs Values
timeFrame: Up to Week 52
measure: Number of Participants With TEAE Related to Electrocardiograms (ECG)
timeFrame: Up to Week 52
measure: Number of Participants With TEAE Related to Body Weight (Weight Decreased)
timeFrame: Up to Week 52
measure: Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Total Score
timeFrame: Baseline and Week 52 (LOCF)
measure: Change From Baseline in MDS-UPDRS Part III Total Score
timeFrame: Baseline and Week 52 (LOCF)
measure: Change From Baseline to Week 52 (LOCF) in Mean Daily OFF-time
timeFrame: Baseline and Week 52 (LOCF)
Other outcomes:
Locations:
city: Nagoya
country: Japan
state: Aichi
city: Matsuyama
country: Japan
state: Ehime
city: Fukuoka
country: Japan
state: Fukouka
city: Koriyama
country: Japan
state: Fukushima
city: Sapporo
country: Japan
state: Hokkaido
city: Himeji
country: Japan
state: Hyogo
city: Kobe
country: Japan
state: Hyogo
city: Sanda
country: Japan
state: Hyogo
city: Tsuchiura
country: Japan
state: Ibaragi
city: Ichinoseki
country: Japan
state: Iwate
city: Kawasaki
country: Japan
state: Kanagawa
city: Sagamihara
country: Japan
state: Kanagawa
city: Yokohama
country: Japan
state: Kanagawa
city: Tenri
country: Japan
state: Nara
city: Shimajiri-gun
country: Japan
state: Okinawa
city: Chuo-ku
country: Japan
state: Tokyo
city: Meguro-ku
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Fukuoka
country: Japan
city: Kochi
country: Japan
city: Kyoto
country: Japan
city: Miyazaki
country: Japan
city: Osaka
country: Japan
city: Yamagata
country: Japan
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: