Clinical trial NCT02337738: A Phase 2/3 Study of TVP-1012 at 0.5 mg or 1 mg in Levodopa Treated Parkinson's Disease Participants
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 2/3 Study to Evaluate the Efficacy and Safety of TVP-1012 at 0.5 mg or 1 mg in Levodopa Treated Parkinson's Disease Patients With Wearing Off
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Parkinson's Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-01-14
Enrollment: 404
Sex: ALL
Minimum age (years): 30
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of TVP-1012 (0.5 mg or 1 mg/day) as an add-on to levodopa in Japanese participants with Parkinson's disease with wearing-off phenomenon.

Detailed description: This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, phase 2/3 study to evaluate the efficacy and safety of TVP-1012 as an add-on to levodopa in Japanese participants with Parkinson's disease with wearing-off phenomenon.

The study period consisted of a 28-week trial period. The participants who fulfilled the inclusion criteria and did not meeting any of the exclusion criteria were enrolled, and randomized in a 1:1:1 ratio to the 0.5 mg of TVP-1012, the 1 mg of TVP-1012, or the placebo group. In each treatment group, participants received 0.5 mg of TVP-1012, 1 mg of TVP-1012, or placebo once daily in a double-blinded manner.

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 Modified Hoehn \& Yahr stage 2 to 4 (in the "Off" state) at the start of the run-in period.
* The participant has wearing off phenomenon and has been continuously receiving a levodopa combination drug for \>= 6 months prior to the start of the run-in period.
* The participant has been receiving a levodopa combination drug with a stable dose regimen (dosing frequency, at least 3 times a day) since the start of the run-in period.
* For participants receiving eantacapone concomitantly,the participant has been receiving entacapone with a stable dose regimen from the start of the run-in period.
* For participants receiving a dopamine agonist, anticholinergic drug, amantadine, droxidopa, istradefylline, or zonisamide concomitantly, the participant has been receiving those drugs with a stable dose regimen since 14 days prior to 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.
* The participant has completed patient diary for at least 4 of the 7 days preceding the study visit at the end of the run-in period.
* The participant has mean daily off-time of \>= 2.5 hours at the end of the run-in period

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 unstable systemic disease.
* The participant has severe dyskinesia.
* The participant has Mini-Mental State Examination (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 major depression 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 antagonist 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 has 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: Change From Baseline in Mean Daily OFF-time During Treatment Period
timeFrame: From Baseline to Week 26
Secondary outcomes:
measure: Change From Baseline to Week 26 (LOCF) in Mean Daily OFF-time
timeFrame: Baseline and Week 26 (LOCF)
measure: Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Total Score
timeFrame: Baseline and Week 26 (LOCF)
measure: Change From Baseline in MDS-UPDRS Part III Total Score
timeFrame: Baseline and Week 26 (LOCF)
measure: Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index Score
timeFrame: Baseline and Week 26 (LOCF)
measure: Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score
timeFrame: Baseline and Week 26 (LOCF)
measure: Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 26
measure: Number of Participants With Markedly Abnormal Vital Signs Values
timeFrame: Up to Week 26
measure: Number of Participants With TEAE Related to Body Weight (Weight Decreased)
timeFrame: Up to Week 26
measure: Number of Participants With TEAE Related to Electrocardiograms (ECG) (Sinus Bradycardia)
timeFrame: Up to Week 26
measure: Number of Participants With TEAE Related to Clinical Laboratory Tests
timeFrame: Up to Week 26
Other outcomes:
Locations:
city: Nagoya
country: Japan
state: Aichi
city: Matsuyama
country: Japan
state: Ehime
city: Touon
country: Japan
state: Ehime
city: Kitakyushu
country: Japan
state: Fukuoka
city: Onoshiro
country: Japan
state: Fukuoka
city: Aizuwakamatsu
country: Japan
state: Fukushima
city: Fujioka
country: Japan
state: Gumma
city: Asahikawa
country: Japan
state: Hokkaido
city: Iwamizawa
country: Japan
state: Hokkaido
city: Sapporo
country: Japan
state: Hokkaido
city: Akashi
country: Japan
state: Hyogo
city: Kobe
country: Japan
state: Hyogo
city: Tsukuba
country: Japan
state: Ibaragi
city: Morioka
country: Japan
state: Iwate
city: Takamatsu
country: Japan
state: Kagawa
city: Fujisawa
country: Japan
state: Kanagawa
city: Kawasaki
country: Japan
state: Kanagawa
city: Sagamihara
country: Japan
state: Kanagawa
city: Nankoku
country: Japan
state: Kochi
city: Goshi
country: Japan
state: Kumamoto
city: Sendai
country: Japan
state: Miyagi
city: Matsumoto
country: Japan
state: Nagano
city: Higashisonogi-gun
country: Japan
state: Nagasaki
city: Joetsu
country: Japan
state: Niigata
city: Yufu
country: Japan
state: Oita
city: Higashiosaka
country: Japan
state: Osaka
city: Hirakata
country: Japan
state: Osaka
city: Suita
country: Japan
state: Osaka
city: Takatsuki
country: Japan
state: Osaka
city: Toyonaka
country: Japan
state: Osaka
city: Irima-gun
country: Japan
state: Saitama
city: Fuji
country: Japan
state: Shizuoka
city: Hamamatsu
country: Japan
state: Shizuoka
city: Izunokuni
country: Japan
state: Shizuoka
city: Shimono
country: Japan
state: Tochigi
city: Yoshinogawa
country: Japan
state: Tokushima
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Fuchu
country: Japan
state: Tokyo
city: Kodaira
country: Japan
state: Tokyo
city: Nerima-ku
country: Japan
state: Tokyo
city: Ota-ku
country: Japan
state: Tokyo
city: Setagaya-ku
country: Japan
state: Tokyo
city: Shibuya-ku
country: Japan
state: Tokyo
city: Akita
country: Japan
city: Aomori
country: Japan
city: Chiba
country: Japan
city: Fukuoka
country: Japan
city: Fukushima
country: Japan
city: Hiroshima
country: Japan
city: Kyoto
country: Japan
city: Miyazaki
country: Japan
city: Niigata
country: Japan
city: Okayama
country: Japan
city: Osaka
country: Japan
city: Tokushima
country: Japan
city: Toyama
country: Japan
city: Wakayama
country: Japan
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Hattori N, Takeda A, Hanya Y, Kitagawa T, Arai M, Furusawa Y, Mochizuki H, Nagai M, Takahashi R. Effects of rasagiline on Parkinson's Disease Questionnaire (PDQ-39) emotional well-being domain in patients with Parkinson's disease: A post-hoc analysis of clinical trials in Japan. PLoS One. 2022 Jan 25;17(1):e0262796. doi: 10.1371/journal.pone.0262796. eCollection 2022.