Parkinson Disease
Conditions
Brief summary
To evaluate the safety, tolerability, pharmacokinetics, and efficacy of the Lu AE04621 and metabolite after ascending oral doses of Lu AE04621 in patients with Parkinson's Disease.
Detailed description
The study comprised 5 cohorts (Cohorts 1 to 5), with each cohort consisting of 3 patients with Parkinson's disease (men and/or women). Each patient will be treated for 3 or 4 days, with increasing dose each day. Dosing regimen will be decided at a dosing conferences. Dose levels can be increased, maintained or reduced both between cohorts but also within same cohort. The results are presented by dose level and reflect the actual doses administered. A follow-up safety visit was scheduled approximately 7 days after the last dose of IMP.
Interventions
DRUG0.04 mg Lu AE04621
0.04 mg dose group
DRUG0.08 mg Lu AE04621
0.08mg dose group
DRUG0.2 mg Lu AE04621
0.2 mg dose group
DRUG0.4 mg Lu AE04621
0.4 mg dose group
DRUG0.6 mg Lu AE04621
0.6 mg dose group
DRUG0.8 mg Lu AE04621
0.8 mg dose group
DRUG1.0 mg Lu AE04621
1.0 mg dose group
DRUG1.2 mg Lu AE04621
1.2 mg dose group
Sponsors
H. Lundbeck A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study comprised 5 cohorts (Cohorts 1 to 5), with each cohort consisting of 3 patients (men and/or women). The dosing regimen planned for Cohort 1 was a dose of 0.2 mg Lu AE04621 on Day 1 followed by a dose of 0.4 mg Lu AE04621 on Day 2, and a dose of 0.6 mg Lu AE04621 on Day 3. • The dosing regimen planned for Cohort 2 was 0.4 mg Lu AE04621 on Day 1 followed by a dose of 0.6 mg Lu AE04621 on Day 2, and a dose of 0.8 mg Lu AE04621 on Day 3. The dosing regimen planned for Cohort 3 was 0.2 mg Lu AE04621 on Day 1 followed by a dose of 0.4 mg Lu AE04621 on Day 2, a dose of 0.6 mg Lu AE04621 on Day 3, and a dose of 1.0 mg Lu AE04621 on Day 4. The dosing regimen planned for Cohorts 4 and 5 was 0.2 mg Lu AE04621 on Day 1 followed by a dose of 0.4 mg Lu AE04621 on Day 2, a dose of 0.6 mg Lu AE04621 on Day 3, and a dose of 1.2 mg Lu AE04621 on Day 4. The results are presented by dose groups and are based on the actual doses administered.
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* The patient is diagnosed with idiopathic Parkinson Disease (consistent with the UK Parkinson's Disease Society Brain Bank Criteria for the Diagnosis of PD). * The patient's Hoehn and Yahr Staging score is ≤ 3 in the ON state. * The patient experiences motor fluctuations with at least 2.5 hours of OFF periods in the awake time and has predictable morning OFF episodes, which have been consistent within the past 4 weeks. * The patient currently has a good response to L-DOPA and has been receiving a stable dose of L-DOPA (≥3 doses per day of standard L-DOPA or ≥3 doses per day of Carbidopa and L-DOPA, Extended-Release Capsules) during at least four weeks prior to screening.
Exclusion criteria
* The patient has cognitive impairment, defined as a Mini Mental State Examination(MMSE) score ≤ 26 at the Screening Visit. * The patient has severe disabling dyskinesia * The patient takes or has taken disallowed recent or concomitant medication (CYP2D6 inhibitors, CYP 3A4 substrate, Dopamine agonists, 5 HT3 antagonists, Anti-viral (Amantadine)) Other protocol defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG) | Baseline to day 11 | Number of patients with an adverse event |
| Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) for Lu AE04621 | From dosing to up to 24 hours after dosing | — |
| Maximum Observed Concentration (Cmax) for Lu AE04621 | From dosing to up to 24 hours after dosing | — |
| Apparent Elimination Half-life of Lu AE04621 in Plasma (t½) | From dosing to up to 24 hours after dosing | — |
| Time to Onset of ON Time After Lu AE04621 Administration | From dosing to 90 minutes after dosing | ON state is defined as a period of good control of parkinsonian features with relatively good overall function and mobility. Motor fluctuation assessments are patient-reported outcomes, and guidance will be given to the patients on how to complete them. Date and time will be registered when the patient turns to ON and OFF state. OFF state is defined as a period of poor control of parkinsonian features with relatively poor overall function, such as worsening tremor, rigidity, balance or bradykinesia. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON'. |
| Duration of ON Time | From dosing up to 24h post-dose | ON state is defined as a period of good control of parkinsonian features with relatively good overall function and mobility. Motor fluctuation assessments are patient-reported outcomes, and guidance will be given to the patients on how to complete them. Date and time will be registered when the patient turns to ON and OFF state. OFF state is defined as a period of poor control of parkinsonian features with relatively poor overall function, such as worsening tremor, rigidity, balance or bradykinesia. Outcome measured in minutes. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON' following administration of Lu AE04621. |
Countries
United States
Participant flow
Pre-assignment details
Groups are overlapping the cohorts
Participants by arm
| Arm | Count |
|---|---|
| Lu AE04621 Patients having received 3 or 4 doses of Lu AE04621, ranging from 0.04 to 1.2 mg. Baseline measures are anlayzed on full patient group only. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Lu AE04621 |
|---|---|
| Age, Continuous | 63 years STANDARD_DEVIATION 5.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 11 | 0 / 14 | 0 / 12 | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 1 | 0 / 1 | 2 / 11 | 7 / 14 | 3 / 12 | 3 / 3 | 1 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 11 | 0 / 14 | 0 / 12 | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Apparent Elimination Half-life of Lu AE04621 in Plasma (t½)
Time frame: From dosing to up to 24 hours after dosing
Population: The overall number of participants analyzed in each group represents the number of dosing occasion at a particular dose, minus occasions with missing or unreliable data. The results are reported for the dose groups with sufficient data to calculate the parameter (missing dose groups for t½ are: 0.04, 0.08, 0.8, 1.0 and 1.2 mg)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04 mg Lu AE04621 | Apparent Elimination Half-life of Lu AE04621 in Plasma (t½) | 3.24 hour | Standard Deviation 2.43 |
| 0.08 mg Lu AE04621 | Apparent Elimination Half-life of Lu AE04621 in Plasma (t½) | 5.00 hour | Standard Deviation 2.51 |
| 0.2 mg Lu AE04621 | Apparent Elimination Half-life of Lu AE04621 in Plasma (t½) | 4.11 hour | Standard Deviation 2.01 |
Primary
Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) for Lu AE04621
Time frame: From dosing to up to 24 hours after dosing
Population: The overall number of participants analyzed in each group represents the number of dosing occasion at a particular dose, minus occasions with missing or unreliable data. The results are reported for the dose groups with sufficient data to calculate the parameter (missing dose groups for AUC(0-24 hours) are: 0.04, 0.08, 0.8, 1.0 and 1.2 mg)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04 mg Lu AE04621 | Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) for Lu AE04621 | 212 pgxh/mL | Standard Deviation 268 |
| 0.08 mg Lu AE04621 | Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) for Lu AE04621 | 292 pgxh/mL | Standard Deviation 219 |
| 0.2 mg Lu AE04621 | Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) for Lu AE04621 | 309 pgxh/mL | Standard Deviation 276 |
Primary
Duration of ON Time
ON state is defined as a period of good control of parkinsonian features with relatively good overall function and mobility. Motor fluctuation assessments are patient-reported outcomes, and guidance will be given to the patients on how to complete them. Date and time will be registered when the patient turns to ON and OFF state. OFF state is defined as a period of poor control of parkinsonian features with relatively poor overall function, such as worsening tremor, rigidity, balance or bradykinesia. Outcome measured in minutes. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON' following administration of Lu AE04621.
Time frame: From dosing up to 24h post-dose
Population: Each patient received 3 or 4 doses of Lu AE04621. The overall number analyzed in each group represents the number of dosing occasion at a particular dose when patients turned 'ON'. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04 mg Lu AE04621 | Duration of ON Time | 203 minutes | Standard Deviation 152.9 |
| 0.08 mg Lu AE04621 | Duration of ON Time | 249 minutes | Standard Deviation 98.9 |
| 0.2 mg Lu AE04621 | Duration of ON Time | 270 minutes | Standard Deviation 124.7 |
| 0.4 mg Lu AE04621 | Duration of ON Time | 87 minutes | Standard Deviation 0 |
| 0.6 mg Lu AE04621 | Duration of ON Time | 401 minutes | Standard Deviation 209.3 |
Primary
Maximum Observed Concentration (Cmax) for Lu AE04621
Time frame: From dosing to up to 24 hours after dosing
Population: Each patient received 3 or 4 doses of Lu AE04621. The overall number of participants analyzed in each group represents the number of dosing occasion at a particular dose, minus occasions with missing or unreliable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04 mg Lu AE04621 | Maximum Observed Concentration (Cmax) for Lu AE04621 | 3.52 pg/mL | Standard Deviation 0 |
| 0.08 mg Lu AE04621 | Maximum Observed Concentration (Cmax) for Lu AE04621 | 6.31 pg/mL | Standard Deviation 0 |
| 0.2 mg Lu AE04621 | Maximum Observed Concentration (Cmax) for Lu AE04621 | 48.6 pg/mL | Standard Deviation 69.9 |
| 0.4 mg Lu AE04621 | Maximum Observed Concentration (Cmax) for Lu AE04621 | 60.4 pg/mL | Standard Deviation 57.3 |
| 0.6 mg Lu AE04621 | Maximum Observed Concentration (Cmax) for Lu AE04621 | 52.8 pg/mL | Standard Deviation 48.5 |
| 0.8 mg Lu AE04621 | Maximum Observed Concentration (Cmax) for Lu AE04621 | 29.8 pg/mL | Standard Deviation 31.3 |
| 1.0 mg Lu AE04621 | Maximum Observed Concentration (Cmax) for Lu AE04621 | 55.9 pg/mL | Standard Deviation 60.7 |
| 1.2 mg Lu AE04621 | Maximum Observed Concentration (Cmax) for Lu AE04621 | 237 pg/mL | Standard Deviation 67.9 |
Primary
Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG)
Number of patients with an adverse event
Time frame: Baseline to day 11
Population: Each patient received 3 or 4 doses of Lu AE04621. The overall number of participants analyzed in each group represents the number of patients having received a particular dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.04 mg Lu AE04621 | Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG) | 0 Participants |
| 0.08 mg Lu AE04621 | Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG) | 0 Participants |
| 0.2 mg Lu AE04621 | Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG) | 2 Participants |
| 0.4 mg Lu AE04621 | Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG) | 7 Participants |
| 0.6 mg Lu AE04621 | Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG) | 3 Participants |
| 0.8 mg Lu AE04621 | Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG) | 3 Participants |
| 1.0 mg Lu AE04621 | Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG) | 1 Participants |
| 1.2 mg Lu AE04621 | Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG) | 1 Participants |
Primary
Time to Onset of ON Time After Lu AE04621 Administration
ON state is defined as a period of good control of parkinsonian features with relatively good overall function and mobility. Motor fluctuation assessments are patient-reported outcomes, and guidance will be given to the patients on how to complete them. Date and time will be registered when the patient turns to ON and OFF state. OFF state is defined as a period of poor control of parkinsonian features with relatively poor overall function, such as worsening tremor, rigidity, balance or bradykinesia. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON'.
Time frame: From dosing to 90 minutes after dosing
Population: Each patient received 3 or 4 doses of Lu AE04621. The overall number of participants analyzed in each group represents the number of dosing occasion at a particular dose. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04 mg Lu AE04621 | Time to Onset of ON Time After Lu AE04621 Administration | 35 minutes | Standard Deviation 20.4 |
| 0.08 mg Lu AE04621 | Time to Onset of ON Time After Lu AE04621 Administration | 41 minutes | Standard Deviation 28.6 |
| 0.2 mg Lu AE04621 | Time to Onset of ON Time After Lu AE04621 Administration | 39 minutes | Standard Deviation 22.7 |
| 0.4 mg Lu AE04621 | Time to Onset of ON Time After Lu AE04621 Administration | 17 minutes | Standard Deviation 0 |
| 0.6 mg Lu AE04621 | Time to Onset of ON Time After Lu AE04621 Administration | 20 minutes | Standard Deviation 17 |