Parkinson's Disease
Conditions
Brief summary
The purpose of this study is to evaluate the long-term safety of TVP-1012 (1 mg/day) in Japanese participants with early Parkinson's disease.
Detailed description
This is a multicenter, open-label, long-term, extension, phase 3 study to evaluate the safety and efficacy of long-term administration of TVP-1012 at 1 mg for another 26 weeks in participants with early Parkinson's disease who have completed the preceding TVP-1012/CCT-001 (NCT02337725) study. Among participants of the TVP-1012/CCT-001 study, those consenting to participate in this study prior to complete the preceding study and fulfilling the eligibility criteria will be enrolled in this study. From the day after the Visit 8 of the preceding study, participants will receive 1 mg of TVP-1012 once daily for 26 weeks in an unblinded manner.
Interventions
DRUGTVP-1012 1mg
TVP-1012 1mg Tablets
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* The participant has completed the preceding study. * The participant has shown no safety issues during the study treatment in the preceding study, in the opinion of the investigator or subinvestigator.
Exclusion criteria
* The participant has undergone blood collection of \>= 400 mL within 90 days prior to the start of treatment in this study. * The participant is required to take any of the excluded medications or treatments. * The participant is required surgery or hospitalization for surgery during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | Up to 52 weeks | Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With TEAE Related to Clinical Laboratory Tests | Up to 52 weeks | Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks). |
| Number of Participants With Markedly Abnormal Vital Signs Values | Up to 52 weeks | Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Here mmHg is Millimeter of mercury. Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks). |
| Number of Participants With TEAE Related to Electrocardiograms (ECG) (ECG QT Prolonged) | Up to 52 weeks | Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks). |
| Number of Participants With TEAE Related to Body Weight (Weight Loss) | Up to 52 weeks | Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks). |
| Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II + Part III Total Score | Baseline to End of treatment (Week 52) | MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The scales are now titled; (Part I) non-motor experiences of daily living (13 items), (Part II) motor experiences of daily living (13 items), (Part III) motor examination (18 items), and (Part IV) motor complications (six items). Each subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range for Part II+III Total Score was 0-188, with the higher score reflecting the greater severity. Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks). |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 68 investigative sites in Japan, from 10 July 2015 to 14 March 2017.
Pre-assignment details
All participants with Parkinson's disease who completed the 26-week treatment period in preceding study (TVP-1012/CCT-001: NCT02337725) were enrolled in this study. Participants in TVP-1012 group and in Placebo group in preceding study were assigned to TVP-1012+TVP-1012 Group and Placebo+TVP-1012 Group in this study, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + TVP-1012 Group Placebo, once daily, either before or after breakfast in preceding study for 26 weeks, followed by in this study, TVP-1012 (1 mg/day) once daily, either before or after breakfast for 26 weeks. | 95 |
| TVP-1012 + TVP-1012 Group TVP-1012 1 mg, once daily, either before or after breakfast in preceding study for 26 weeks, followed by in this study, TVP-1012 (1 mg/day) once daily, either before or after breakfast for 26 weeks. | 117 |
| Total | 212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator's Judgement | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 5 |
| Overall Study | Pretreatment Event/Adverse Event | 2 | 3 |
| Overall Study | Voluntary Withdrawal | 6 | 8 |
Baseline characteristics
| Characteristic | Placebo + TVP-1012 Group | Total | TVP-1012 + TVP-1012 Group |
|---|---|---|---|
| Age, Continuous | 65.4 Years STANDARD_DEVIATION 9.13 | 66.5 Years STANDARD_DEVIATION 9.09 | 67.4 Years STANDARD_DEVIATION 8.99 |
| BMI | 22.28 kg/meter (m)^2 STANDARD_DEVIATION 2.798 | 22.56 kg/meter (m)^2 STANDARD_DEVIATION 3.09 | 22.78 kg/meter (m)^2 STANDARD_DEVIATION 3.303 |
| Duration of Parkinson's Disease | 1.52 Years STANDARD_DEVIATION 1.223 | 1.77 Years STANDARD_DEVIATION 1.695 | 1.97 Years STANDARD_DEVIATION 1.981 |
| Height | 159.2 Centimeters (cm) STANDARD_DEVIATION 9.28 | 159.0 Centimeters (cm) STANDARD_DEVIATION 9.04 | 158.9 Centimeters (cm) STANDARD_DEVIATION 8.87 |
| MDS-UPDRS Part II + Part III Total Score (Pre-Dose) | 33.0 Scores on a scale STANDARD_DEVIATION 15.86 | 33.8 Scores on a scale STANDARD_DEVIATION 16.44 | 34.4 Scores on a scale STANDARD_DEVIATION 16.95 |
| Modified Hoehn & Yahr Stage | 2.13 Units on a scale STANDARD_DEVIATION 0.627 | 2.16 Units on a scale STANDARD_DEVIATION 0.627 | 2.18 Units on a scale STANDARD_DEVIATION 0.628 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Japan | 95 Participants | 212 Participants | 117 Participants |
| Sex: Female, Male Female | 53 Participants | 117 Participants | 64 Participants |
| Sex: Female, Male Male | 42 Participants | 95 Participants | 53 Participants |
| Smoking Classification Current Smoker | 7 Participants | 12 Participants | 5 Participants |
| Smoking Classification Ex-Smoker | 32 Participants | 81 Participants | 49 Participants |
| Smoking Classification Never Smoked | 56 Participants | 119 Participants | 63 Participants |
| Timing of Study Drug Dose After Breakfast | 47 Participants | 105 Participants | 58 Participants |
| Timing of Study Drug Dose Before Breakfast | 48 Participants | 107 Participants | 59 Participants |
| Weight | 56.68 Kilograms (kg) STANDARD_DEVIATION 9.773 | 57.36 Kilograms (kg) STANDARD_DEVIATION 10.932 | 57.91 Kilograms (kg) STANDARD_DEVIATION 11.803 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 95 | 0 / 117 |
| other Total, other adverse events | 23 / 95 | 49 / 117 |
| serious Total, serious adverse events | 4 / 95 | 6 / 117 |
Outcome results
Primary
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks).
Time frame: Up to 52 weeks
Population: Safety Analysis Set: All participants who received at least 1 dose of TVP-1012 during this study and/or the preceding study (TVP-1012/CCT-001: NCT02337725). The analysis set included 103 participants who enrolled in this study and 14 participants who enrolled only in TVP-1012/CCT-001 and received TVP-1012 (totally 117 participants).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + TVP-1012 Group | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 51 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 91 Participants |
Secondary
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II + Part III Total Score
MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The scales are now titled; (Part I) non-motor experiences of daily living (13 items), (Part II) motor experiences of daily living (13 items), (Part III) motor examination (18 items), and (Part IV) motor complications (six items). Each subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range for Part II+III Total Score was 0-188, with the higher score reflecting the greater severity. Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks).
Time frame: Baseline to End of treatment (Week 52)
Population: Full Analysis Set (FAS); All randomized participants who received at least one dose of TVP-1012 during this study, 103 participants, and only in the preceding study (TVP-1012/CCT-001: NCT02337725), 14 participants, totally 117 participants. The analyzed numbers for each arm were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + TVP-1012 Group | Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II + Part III Total Score | -2.8 Units on a Scale | Standard Deviation 6.01 |
| TVP-1012 + TVP-1012 Group | Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II + Part III Total Score | -2.8 Units on a Scale | Standard Deviation 9.62 |
Secondary
Number of Participants With Markedly Abnormal Vital Signs Values
Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Here mmHg is Millimeter of mercury. Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks).
Time frame: Up to 52 weeks
Population: Safety Analysis Set: All participants who received at least 1 dose of TVP-1012 during this study, 103 participants, and only in the preceding study (TVP-1012/CCT-001: NCT02337725), 14 participants, totally 117 participants.~The number of participants analyzed for each items are participants evaluable for each item within the safety analysis set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature <35.6 Celsius (ºC) | 13 Participants |
| Placebo + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature >37.7 ºC | 0 Participants |
| Placebo + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Systolic Blood Pressure <90 mmHg | 3 Participants |
| Placebo + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure <50 mmHg | 4 Participants |
| Placebo + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure >100 mmHg | 6 Participants |
| Placebo + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Pulse <45 Beats per Minute (bpm) | 0 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure >100 mmHg | 13 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature <35.6 Celsius (ºC) | 30 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure <50 mmHg | 0 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature >37.7 ºC | 1 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Pulse <45 Beats per Minute (bpm) | 1 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With Markedly Abnormal Vital Signs Values | Systolic Blood Pressure <90 mmHg | 3 Participants |
Secondary
Number of Participants With TEAE Related to Body Weight (Weight Loss)
Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks).
Time frame: Up to 52 weeks
Population: Safety Analysis Set: All participants who received at least 1 dose of TVP-1012 during this study and/or the preceding study (TVP-1012/CCT-001: NCT02337725). The analysis set included 103 participants who enrolled in this study and 14 participants who enrolled only in TVP-1012/CCT-001 and received TVP-1012 (totally 117 participants).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Body Weight (Weight Loss) | 1 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Body Weight (Weight Loss) | 0 Participants |
Secondary
Number of Participants With TEAE Related to Clinical Laboratory Tests
Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks).
Time frame: Up to 52 weeks
Population: Safety Analysis Set: All participants who received at least 1 dose of TVP-1012 during this study and/or the preceding study (TVP-1012/CCT-001: NCT02337725). The analysis set included 103 participants who enrolled in this study and 14 participants who enrolled only in TVP-1012/CCT-001 and received TVP-1012 (totally 117 participants).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood Creatine Phosphokinase Increased | 0 Participants |
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood Triglycerides Increased | 1 Participants |
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood Urine Present | 1 Participants |
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | C-Reactive Protein Increased | 0 Participants |
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Glycosylated Haemoglobin Increased | 0 Participants |
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Liver Function Test Abnormal | 0 Participants |
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Liver Function Test Increased | 0 Participants |
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | White Blood Cell Count Increased | 1 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | White Blood Cell Count Increased | 0 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood Creatine Phosphokinase Increased | 1 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Glycosylated Haemoglobin Increased | 1 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood Triglycerides Increased | 0 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Liver Function Test Increased | 1 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood Urine Present | 0 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | Liver Function Test Abnormal | 1 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Clinical Laboratory Tests | C-Reactive Protein Increased | 1 Participants |
Secondary
Number of Participants With TEAE Related to Electrocardiograms (ECG) (ECG QT Prolonged)
Reported data was the number collected from the first dose of TVP-1012 to the end of study (up to 52 weeks). Timeframe was 52 weeks that was total duration of both this study (26 weeks) and the preceding study (TVP-1012/CCT-001: NCT02337725; 26 weeks).
Time frame: Up to 52 weeks
Population: Safety Analysis Set: All participants who received at least 1 dose of TVP-1012 during this study and/or the preceding study (TVP-1012/CCT-001: NCT02337725). The analysis set included 103 participants who enrolled in this study and 14 participants who enrolled only in TVP-1012/CCT-001 and received TVP-1012 (totally 117 participants).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + TVP-1012 Group | Number of Participants With TEAE Related to Electrocardiograms (ECG) (ECG QT Prolonged) | 1 Participants |
| TVP-1012 + TVP-1012 Group | Number of Participants With TEAE Related to Electrocardiograms (ECG) (ECG QT Prolonged) | 1 Participants |