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CompletedNCT03391882Updated Dec 16, 2022Results posted

A Study of an Investigational Drug to See How it Affects the People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes) Compared to an Approved Drug Used to Treat People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)

A Phase 3 interventional study of APL-130277 and subcutaneous apomorphine in Motor OFF Episodes Associated With Parkinson's Disease, sponsored by Sumitomo Pharma America, Inc.. Completed at 31 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-12-16.

Sponsored by Sumitomo Pharma America, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
113
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

A study of an investigational drug to see how it affects the people with Parkinson's Disease complicated by motor fluctuations ("OFF" Episodes) compared to an approved drug used to treat people with Parkinson's Disease complicated by motor fluctuations ("OFF" Episodes)

Read the detailed description

An Open-Label, Randomized, Crossover Trial utilizing a Single-Blinded Rater to evaluate APL-130277 compared to s.c. Apomorphine in Levodopa Responsive Subjects with Parkinson's Disease Complicated by Motor Fluctuations.

PART A consists of an open label, crossover titration phase where eligible subjects will be randomized to 1 of 2 treatment sequences in a 1:1 ratio to Sublingual APL-130277 followed by subcutaneous apomorphine or subcutaneous apomorphine followed by sublingual APL-130277. Subjects will undergo dose titration with the first study treatment (APL-130277 or sc apomorphine) to tolerance and effect, ie, the tolerable dose that turns the subject from the practically defined "OFF" state to the full "ON" state as determined by both the Investigator and subject. The subject will then be crossed over to the other study treatment (APL-130277 or subcutaneous apomorphine) and similarly titrated to tolerance and effect. These determined doses of APL-130277 and subcutaneous apomorphine will be used during PART B.

PART B consists of an open-label, crossover treatment period where subjects will be randomized to one of the study treatment for 4 weeks, then be crossed over to the other study treatment (APL-130277 or sc apomorphine) for additional 4-weeks of open-label treatment. Subjects return to the clinic for safety and efficacy assessments throughout the treatment period.

This study is designed to test the superiority of sublingually administered APL-130277 against subcutaneously injected apomorphine (APO-go) for the treatment of "OFF" episodes in patients with Parkinson's Disease, as measured by the change from pre-dose to 90 minutes post-dose in MDS UPDRS Part III score in Part B after 4 weeks of dosing in each crossover period.

02

Conditions studied

  • Motor OFF Episodes Associated With Parkinson's Disease

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Keywords

  • Parkinson's Disease
  • "Off" Episodes
  • motor fluctuations associated with Parkinson's Disease
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. The subject (and caregiver, if applicable) must be fully informed of and understand the objectives, procedures, and possible benefits and risks of the study, and give written informed consent prior to performing any study related activities.
  2. Male or female ≥ 18 years of age.
  3. Clinical diagnosis of Idiopathic Parkinson's disease (PD), consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
  4. Clinically meaningful response to levodopa (L-Dopa), as determined by the Investigator.
  5. Subjects at screening must demonstrate an adequate L-Dopa response on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS) Part III in the "ON" state compared to the MDS UPDRS Part III in the "OFF" state and on the Hoehn and Yahr, as determined during the review by Enrollment Adjudication Committee (EAC), Sponsor, and Medical Monitor.
  6. Receiving stable doses of L Dopa/carbidopa and/or L Dopa/benserazide and/or L Dopa/carbidopa/entacapone (immediate or chronic release) administered at least 4 times per day OR Rytary™ administered at least 3 times per day for at least 4 weeks before the initial screening Visit (SV1). Adjunctive PD medication regimens are permitted but must be maintained at a stable dose for at least 4 weeks prior to SV1 with the exception of monoamine oxidase B (MAO B) inhibitors, which must be maintained at a stable level for at least 8 weeks prior to SV1.
  7. No planned medication change(s) or surgical intervention anticipated during the course of study.
  8. Subjects must experience at least one well defined "OFF" episode per day and have a total daily "OFF" time duration of > 2 hours during the waking day, based on judgment of physician and subject self assessment.
  9. Subject must have predictable morning "OFF" periods, based on judgment of physician and subject self assessment.
  10. Subject, and where appropriate caregiver, must be trained in completing the home dosing diaries and able to recognize "ON" and "OFF" states.
  11. Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
  12. Mini-Mental State Examination (MMSE) score > 25.
  13. Female subject of childbearing potential and male subject with female partner of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and for at least 7 days after the last dose of study drug has been taken. Note: Continued use of adequate and reliable contraception is recommended through 30 days after study completion.
  14. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study related procedures to complete the study.
  15. Must be approved as a satisfactory candidate by the Enrollment Adjudication Committee (EAC), Medical Monitor, and Sponsor.

Exclusion criteria

Exclusion Criteria:

  1. Atypical or secondary parkinsonism.
  2. Major focal brain disorders including malignancy or stroke.
  3. Prior treatment with any of the following: a neurosurgical procedure for PD; continuous subcutaneous (subcutaneous) apomorphine infusion; subcutaneous (subcutaneous) apomorphine injection; Duodopa/Duopa; or APL-130277.
  4. Contraindications to domperidone, subcutaneous apomorphine, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of subcutaneous apomorphine (notably sodium metabisulfite).
  5. Female who is pregnant or lactating.
  6. Participation in an interventional clinical study and/or receipt of any investigational (ie, unapproved) medication within 30 days prior to SV1.
  7. Currently taking selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or clozapine) or dopamine depleting agents. Subjects receiving anti depressants must be on a stable daily dose for at least 8 weeks prior to SV1.
  8. The subject has a current diagnosis or history of substance abuse (excluding nicotine and caffeine) or alcohol abuse (in the opinion of the investigator) \< 6 months prior to SV1.
  9. The recreational use of cannabinoids and hallucinogenic are excluded, as well any use of a sublingual formulation of any drug.
  10. Subject has a history of malignancy within 5 years prior to SV1, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
  11. Subject has a clinically significant abnormality on screening evaluation including physical examination, vital signs, electrocardiogram (ECG), or laboratory tests that the Investigator considers to be inappropriate to allow participation in the study.
  12. Subject has screening laboratory test results of: blood urea nitrogen (BUN) value ≥ 1.5 times the upper limit of normal (ULN) for the reference range; serum creatinine > 1.5 times the ULN for the reference range; or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥ 2 times the ULN for the reference laboratory.
  13. Subject has random (non-fasting) screening glucose of ≥ 200 mg/dL (11.1 mmol/L) or HbA1c > 7.0%.
  14. Subjects with type 1 diabetes, or insulin dependent diabetics are excluded. Subjects with type 2 diabetes are eligible for study inclusion if the following conditions are met:

    • Subject's screening glucose is \< 200 mg/dL (11.1 mmol/L). Note: Subjects with random (non fasting) blood glucose at screening ≥ 200 mg/dL (11.1 mmol/L) must be retested in a fasted state; and
    • Subject's hemoglobin A1c (HbA1c) ≤ 7.0%; and
    • If the subject is currently being treated with oral anti-diabetic medication(s), the dose must have been stable for at least 4 weeks prior to SV1. Such medication may be adjusted or discontinued during the study, as clinically indicated.
  15. The subject's screening ECG results of corrected QT interval using Fridericia's formula (QTcF) ≥ 450 msec for male subjects or ≥ 470 msec for female subjects. Eligibility will be based on the core laboratory ECG interpretation report.
  16. Subject has a positive screening laboratory test result for human immunodeficiency virus (HIV).
  17. Subject has a positive screening laboratory test result for hepatitis B surface antigen or hepatitis C antibodies and has liver function test results at screening above the ULN for the reference laboratory.
  18. Subject has any other medical disorder that, in the opinion of the Investigator, could interfere with the subject's participation in the study.
  19. Subject has major psychiatric disorder(s), including but not limited to: bipolar disorder, psychosis (eg, Parkinson's Disease Psychosis), major depressive episode, or any disorder that, in the opinion of the Investigator, would require treatment that could make study participation unsafe or make treatment compliance difficult.
  20. History of clinically significant impulse control disorder(s).
  21. History of symptomatic orthostatic hypotension requiring medication.
  22. History of severe dyskinesia based on a score of 4 on the MDS-UPDRS Part IV.
  23. Dementia that precludes providing informed consent or would interfere with participation in the study.
  24. Current/recent suicidal ideation as evidenced by answering "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS assessment at screening (using the "screening /Baseline Version" scale, in the past 12 months) or attempted suicide within the last 5 years.
  25. Presence of canker or mouth sores in the 30 days prior to SV1, or other clinically significant oral pathology in the opinion of the Investigator. The Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling a subject into the study
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
113 participants (actual)

Study arms

  • Experimental
    APL-130277

    APL-130277: Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A

    Drug: APL-130277

  • Active comparator
    subcutaneous apomorphine

    subcutaneous apomorphine , Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A

    Drug: subcutaneous apomorphine

Interventions

  • DrugAPL-130277

    APL-130277: Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A

    Also known as: Apomorphine Hydrochloride

  • Drugsubcutaneous apomorphine

    subcutaneous apomorphine Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A

    Also known as: APO-go®

05

What researchers measure

Primary outcomes

  1. Change From Pre-dose to 90 Mins. Post-dose in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Score After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).

    The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. The summary score used in this study for the primary objective and primary efficacy endpoint is Part III motor examination score. Each Part III item has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4. The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).

    Time frame: Pre-dose to 90 minutes post-dose at Week 4 of each treatment period (Visit 3 and 6)

Secondary outcomes

  1. Durability of Effect, Defined as an Investigator Confirmed Full "ON" Within 30 Minutes Post Dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).

    Investigator will confirm whether subject is "OFF", Full "ON" or Partial "ON" , and note the time the subject changes from "OFF" to Partial "ON" or Full "ON". The Investigator will also record the subject "ON"/"OFF" status (binary variable, Yes / No) prior to performing each MDS-UPDRS Part III assessment. Durability of effect is defined as an Investigator confirmed full "ON" within 30 minutes post-dose and at 90 minutes post-dose, after 4 weeks of dosing in each PART B crossover period. Response rate = % of subjects that achived full "ON" within the timeframe

    Time frame: Within 30 minutes post-dose and at 90 minutes post-dose at Week 4 of each treatment period (Visit 3 and 6)

  2. Subject Preference for APL Treatment as Measured by the Subject Treatment Preference Questionnaire (TPQ), Planned After the Subject Had Completed Both APL-130277 and sc Apomorphine Treatment Regimens (Assessed In-clinic at Visit 6 of PART B)

    The TPQ assessment of subject treatment preference was changed from being based on a visual analogue scale or VAS (Q9b)) to a 5-point Likert scale (Q9a). Subject reported preference for APL or SC was based on question Q9a or Q9b combined. For Q9a, responses were dichotomized as follows for statistical analysis: preference for APL (responses of either definitely or somewhat prefer APL) versus no preference for APL (responses of no preference, or somewhat/definitely prefer sc apomorphine). The VAS score was similarly dichotomized as preference for APL (score of \>0 to 50) versus no preference for APL (-50 to 0). If a subject responded to both Q9a and Q9b, then Q9a only was used.

    Time frame: After 8 weeks of treatment (Visit 6)

  3. Subject Confirmed Durability of Effect, Defined as Subject Confirmed Full "ON" Within 30 Minutes Post-dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).

    Patients will confirm whether he/she is "OFF", Full "ON" or Partial "ON", and the staff will ask the subject to notify the staff when he/she changes from "OFF" to Partial "ON" or Full "ON" (binary variable, Yes / No) . Subject confirmed durability of effect is defined as subject confirmed full "ON" within 30 minutes post-dose and at 90 minutes post-dose, after 4 weeks of dosing in each crossover period (assessed in-clinic at V3 and V6 of PART B). Response rate = % subjects that achived full ON within the timeframe

    Time frame: Week 4

  4. Patient Global Impression of Change (PGI-C): Subject Improvement of "OFF" Episodes, Defined as Very Much Better, Much Better or a Little Better After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).

    The PGI-C is the patient reported outcome counterpart to the Clinical Global Impressions scale, (CGI), which was published in 1976 by the National Institute of Mental Health (US). It consists of one item taken from the CGI and adapted to the patient. The PGI-C is based on a 7-point scale, where a lower score is associated with higher symptom improvement. The scale is: Very much better Much better A little better No change A little worse Much worse Very much worse Subject improvement of "OFF" episodes is defined as very much better, much better or a little better at Week 4 in each PART B crossover period. Response rate= % of subjects who achieved improvement of "OFF" episodes

    Time frame: At Week 4 of each treatment period (Visit 3 and 6, or Early Termination)

06

Results

Posted Dec 16, 2022

Participant flow

Study Overall
Participant flow — Study Overall
MilestoneAPL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APL
Started201919181819
Safety population201819181819
Modified intent-to-treat population201819181819
Completed0016151415
Not completed20193344
Withdrew: Adverse event361131
Withdrew: Lack of efficacy1390000
Withdrew: Withdrawal by subject332213
Withdrew: Early term at sponsor request010000
Withdrew: Protocol violation100000
Part A - Titration Phase
Participant flow — Part A - Titration Phase
MilestoneAPL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APL
Started201919181819
Safety population part a201819181819
Modified intent-to-treat population part a201819181819
Completed2319181819
Not completed18160000
Withdrew: Adverse event360000
Withdrew: Lack of efficacy1260000
Withdrew: Withdrawal by subject330000
Withdrew: Early term at sponsor request010000
Post Part A / Pre Part B
Participant flow — Post Part A / Pre Part B
MilestoneAPL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APL
Started2319181819
Completed0019181819
Not completed230000
Withdrew: Lack of efficacy130000
Withdrew: Protocol violation100000
Part B - Treatment Phase
Participant flow — Part B - Treatment Phase
MilestoneAPL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APL
Started0019181819
Safety population part b0019181819
Modified intent-to-treat population part b0019181819
Completed0016151415
Not completed003344
Withdrew: Adverse event001131
Withdrew: Withdrawal by subject002213

Outcome measures

PrimaryChange From Pre-dose to 90 Mins. Post-dose in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Score After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).

The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. The summary score used in this study for the primary objective and primary efficacy endpoint is Part III motor examination score. Each Part III item has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4. The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).

Time frame:
Pre-dose to 90 minutes post-dose at Week 4 of each treatment period (Visit 3 and 6)
Reported as:
Least squares mean · Units on a scale
Change From Pre-dose to 90 Mins. Post-dose in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Score After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).
Units on a scaleSC (Subcutaneous Apomorphine)APL (APL-130277)
Change From Pre-dose to 90 Mins. Post-dose in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Score After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).-13.78 (-16.65 to -10.90)-13.55 (-16.39 to -10.70)
Statistical analysis
  • SC (Subcutaneous Apomorphine) vs APL (APL-130277) · Mixed Models Analysis · p = 0.8944 · Mean difference (final values): 0.23 · 95% CI -3.16 to 3.62
SecondaryDurability of Effect, Defined as an Investigator Confirmed Full "ON" Within 30 Minutes Post Dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).

Investigator will confirm whether subject is "OFF", Full "ON" or Partial "ON" , and note the time the subject changes from "OFF" to Partial "ON" or Full "ON". The Investigator will also record the subject "ON"/"OFF" status (binary variable, Yes / No) prior to performing each MDS-UPDRS Part III assessment. Durability of effect is defined as an Investigator confirmed full "ON" within 30 minutes post-dose and at 90 minutes post-dose, after 4 weeks of dosing in each PART B crossover period. Response rate = % of subjects that achived full "ON" within the timeframe

Time frame:
Within 30 minutes post-dose and at 90 minutes post-dose at Week 4 of each treatment period (Visit 3 and 6)
Reported as:
Number · Percentage of participants
Durability of Effect, Defined as an Investigator Confirmed Full "ON" Within 30 Minutes Post Dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).
Percentage of participantsSC (Subcutaneous Apomorphine)APL (APL-130227)
Durability of Effect, Defined as an Investigator Confirmed Full "ON" Within 30 Minutes Post Dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).18.0317.74
Statistical analysis
  • SC (Subcutaneous Apomorphine) vs APL (APL-130227) · generalized linear random effects model · p = 0.7777 · Odds ratio (or): 1.129 · 95% CI 0.484 to 2.637
SecondarySubject Preference for APL Treatment as Measured by the Subject Treatment Preference Questionnaire (TPQ), Planned After the Subject Had Completed Both APL-130277 and sc Apomorphine Treatment Regimens (Assessed In-clinic at Visit 6 of PART B)

The TPQ assessment of subject treatment preference was changed from being based on a visual analogue scale or VAS (Q9b)) to a 5-point Likert scale (Q9a). Subject reported preference for APL or SC was based on question Q9a or Q9b combined. For Q9a, responses were dichotomized as follows for statistical analysis: preference for APL (responses of either definitely or somewhat prefer APL) versus no preference for APL (responses of no preference, or somewhat/definitely prefer sc apomorphine). The VAS score was similarly dichotomized as preference for APL (score of \>0 to 50) versus no preference for APL (-50 to 0). If a subject responded to both Q9a and Q9b, then Q9a only was used.

Time frame:
After 8 weeks of treatment (Visit 6)
Reported as:
Number · % of participants
Subject Preference for APL Treatment as Measured by the Subject Treatment Preference Questionnaire (TPQ), Planned After the Subject Had Completed Both APL-130277 and sc Apomorphine Treatment Regimens (Assessed In-clinic at Visit 6 of PART B)
% of participantsOverall
Subject Preference for APL Treatment as Measured by the Subject Treatment Preference Questionnaire (TPQ), Planned After the Subject Had Completed Both APL-130277 and sc Apomorphine Treatment Regimens (Assessed In-clinic at Visit 6 of PART B)72.2 (61.9 to 82.6)
Statistical analysis
  • Overall · binomial distribution with normal approx · p = 0.0002 (The p-value is from a 1-sample, 2-sided test of the null hypothesis that the true proportion preferring APL is 50% to evaluate if a significantly higher proportion of the subjects prefer APL-130277 or not.)
SecondarySubject Confirmed Durability of Effect, Defined as Subject Confirmed Full "ON" Within 30 Minutes Post-dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).

Patients will confirm whether he/she is "OFF", Full "ON" or Partial "ON", and the staff will ask the subject to notify the staff when he/she changes from "OFF" to Partial "ON" or Full "ON" (binary variable, Yes / No) . Subject confirmed durability of effect is defined as subject confirmed full "ON" within 30 minutes post-dose and at 90 minutes post-dose, after 4 weeks of dosing in each crossover period (assessed in-clinic at V3 and V6 of PART B). Response rate = % subjects that achived full ON within the timeframe

Time frame:
Week 4
Reported as:
Number · Percentage of participants
Subject Confirmed Durability of Effect, Defined as Subject Confirmed Full "ON" Within 30 Minutes Post-dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).
Percentage of participantsSC (Subcutaneous Apomorphine)APL (APL-130227)
Subject Confirmed Durability of Effect, Defined as Subject Confirmed Full "ON" Within 30 Minutes Post-dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).14.7519.36
Statistical analysis
  • SC (Subcutaneous Apomorphine) vs APL (APL-130227) · generalized linear random effects model · p = 0.1769 · Odds ratio (or): 1.835 · 95% CI 0.759 to 4.438
SecondaryPatient Global Impression of Change (PGI-C): Subject Improvement of "OFF" Episodes, Defined as Very Much Better, Much Better or a Little Better After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).

The PGI-C is the patient reported outcome counterpart to the Clinical Global Impressions scale, (CGI), which was published in 1976 by the National Institute of Mental Health (US). It consists of one item taken from the CGI and adapted to the patient. The PGI-C is based on a 7-point scale, where a lower score is associated with higher symptom improvement. The scale is: Very much better Much better A little better No change A little worse Much worse Very much worse Subject improvement of "OFF" episodes is defined as very much better, much better or a little better at Week 4 in each PART B crossover period. Response rate= % of subjects who achieved improvement of "OFF" episodes

Time frame:
At Week 4 of each treatment period (Visit 3 and 6, or Early Termination)
Reported as:
Number · Percentage of participants
Patient Global Impression of Change (PGI-C): Subject Improvement of "OFF" Episodes, Defined as Very Much Better, Much Better or a Little Better After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).
Percentage of participantsSC (Subcutaneous Apomorphine)APL (APL-130277)
Patient Global Impression of Change (PGI-C): Subject Improvement of "OFF" Episodes, Defined as Very Much Better, Much Better or a Little Better After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).77.1483.10
Statistical analysis
  • SC (Subcutaneous Apomorphine) vs APL (APL-130277) · generalized linear random effects model · p = 0.3922 · Odds ratio (or): 1.47 · 95% CI 0.61 to 3.53

Adverse events

Collected over 10 weeks (from first dose of study drug to last study visit). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A Dose Titration: APL (APL-130277)0/102 (0%)0/102 (0%)52/102 (51%)
Part A Dose Titration: SC (Subcutaneous Apomorphine)0/97 (0%)1/97 (1%)44/97 (45.4%)
Part B Treatment: APL (APL-130277)0/71 (0%)1/71 (1.4%)23/71 (32.4%)
Part B Treatment: SC (Subcutaneous Apomorphine)0/70 (0%)1/70 (1.4%)37/70 (52.9%)
Most frequent serious events
Most frequent serious events
EventPart A Dose Titration: APL (APL-130277)Part A Dose Titration: SC (Subcutaneous Apomorphine)Part B Treatment: APL (APL-130277)Part B Treatment: SC (Subcutaneous Apomorphine)
Foot fractureInjury, poisoning and procedural complications0/1020/970/711/70
Intestinal obstructionGastrointestinal disorders0/1020/971/710/70
Intestinal ischaemiaGastrointestinal disorders0/1021/970/710/70
Most frequent other events
Most frequent other events
EventPart A Dose Titration: APL (APL-130277)Part A Dose Titration: SC (Subcutaneous Apomorphine)Part B Treatment: APL (APL-130277)Part B Treatment: SC (Subcutaneous Apomorphine)
NauseaGastrointestinal disorders32/10222/9710/7111/70
Injection site haematomaGeneral disorders0/1022/970/7119/70
DyskinesiaNervous system disorders8/1027/978/7114/70
SomnolenceNervous system disorders9/10213/973/714/70
FatigueGeneral disorders6/10210/974/714/70
DizzinessNervous system disorders10/1024/972/713/70
Injection site erythemaGeneral disorders0/1026/971/715/70
Orthostatic hypotensionVascular disorders4/1025/973/714/70
FallInjury, poisoning and procedural complications1/1021/974/711/70
YawningRespiratory, thoracic and mediastinal disorders3/1025/970/711/70

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)APL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APLTotal
<=18 years0000000
Between 18 and 65 years988109852
>=65 years111011891160
Age, Continuous
Age, Continuous(Years)APL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APLTotal
Mean64.9 ± 8.3363.9 ± 9.9965.0 ± 9.8063.2 ± 6.9163.4 ± 9.7165.6 ± 8.6964.4 ± 8.80
Sex: Female, Male
Sex: Female, Male(Participants)APL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APLTotal
Female77616734
Male13111317121278
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)APL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APLTotal
Hispanic or Latino0311218
Not Hispanic or Latino191518161618102
Unknown or Not Reported1001002
Race (NIH/OMB)
Race (NIH/OMB)(Participants)APL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APLTotal
American Indian or Alaska Native0000000
Asian0000000
Native Hawaiian or Other Pacific Islander0000000
Black or African American0000000
White201819181819112
More than one race0000000
Unknown or Not Reported0000000
Country
Country(Participants)APL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APLTotal
Austria1021105
Germany6281051041
Spain78435431
France1100013
United Kingdom11132311
Italy46415121
Baseline Height (cm)
Baseline Height (cm)(cm)APL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APLTotal
Mean168.05 ± 12.626165.62 ± 12.348171.91 ± 10.260174.78 ± 6.632170.94 ± 9.795171.16 ± 9.929170.39 ± 10.652
Baseline Weight (kg)
Baseline Weight (kg)(kg)APL-SCSC-APLAPL-SC-APL-SCAPL-SC-SC-APLSC-APL-APL-SCSC-APL-SC-APLTotal
Mean74.25 ± 16.15170.91 ± 18.62478.45 ± 21.89380.31 ± 11.69183.26 ± 24.38377.14 ± 15.28477.34 ± 18.470

6 further baseline measures are reported on the registry.

07

Study locations

31 sites
  • Medical University Innsbruck, Neurolgy Dept
    Innsbruck, A-6020, Austria
  • Wilhelminenspital, Department of Neurology
    Vienna, A-1160, Austria
  • CHU Caremeau, Service de Neurologie
    Nimes, 30029, France
  • Centre d'Investigation Clinique, CIC 43, CHU Purpan, Hopital Pierre-Paul Riquet, place du Dr. Baylac, Hall D, 2 eme etage -TSA
    Toulouse, 31059, France
  • Klinken Beelitz GmbH Neurologisches Fachkrankenhaus fur Bewegungsstorungen/Parkinson
    Beelitz-Heilstatten, 14547, Germany
  • Charite-University Medicine Berlin, Department of Neurology, Campus charite Mitte
    Berlin, 10117, Germany
  • St. Joseph Krankenhaus Berlin - Weissensee, Abteilung fur Neurologie
    Berlin, 13088, Germany
  • St. Josef Hospital, Klnikum der Ruhr-Universitat-Bochum, Neurologische Klinik
    Bochum, 44791, Germany
  • Universitatsklinikum Carol Gustav Carus an der TU dDresden, Klinik umd Poliklinik fur Neurologie
    Dresden, 01307, Germany
  • Klinik Haag i.OB
    Haag In Oberbayern, 83527, Germany
  • Klinikum rechts der Isar der Technischen Universitat Munchen
    Munchen, 81675, Germany
  • Curiositas ad sanum GmbH
    Munich, 80331, Germany
  • Universitaets-und Rehabillitatinskliniken Ulm
    Ulm, D-89081, Germany
  • San Raffaele Cassino
    Cassino, 03043, Italy
  • University Hospital Policlinico-Vittorio Emanuele, Department "G.F. Ingrassia", Section of Neurosciences
    Catania, Italy
  • A.O.U. Universita degli Studi della Campania "Luigi Vanvitelli" Dipartamento di Scienze Mediche e Chirurgiche Avanzate
    Napoli, 80138, Italy
  • IRCCS San Raffaele Pisana-Clinical Trial Center
    Rome, 00163, Italy
  • Istituto Clinico Humanitas, Dipartmento di Neurologia 1
    Rozzano, 20089, Italy
  • AOU San Giovanni di Dio e Ruggid'Aragona-CEMAND
    Salerno, 84131, Italy
  • Hospital Universitario de Cruces, Neurology
    Barakaldo, Spain
  • Hospital Clinic de Barcelona
    Barcelona, 08036, Spain
  • Hospital de la Santa Creu i Sant Pau c/Mas de Casanovas 90
    Barcelona, 08041, Spain
  • Hospital Universitario de Burgos
    Burgos, 09006, Spain
  • Hospital Universitario de la Princesa
    Madrid, 28006, Spain
  • CINAC, Hospital Universitario HB Pueta del Sur
    Mostoles, 28938, Spain
  • Hospital General de Catalunya
    Sant Cugat del Valles, 08195, Spain
  • King's College Hospital NHS Foundation Trust
    London, SE5 9RS, United Kingdom
  • 10W, Imperial Memory/PD Research Unit, Imperial College Healthcare NHS Trust
    London, W6 8RF, United Kingdom
  • NHS Forth Valley, Pennine Actue NHS Trust, Fairfield General Hospital
    Manchester, Bl9 7TD, United Kingdom
  • Academic Neuroscience Department, C Floor, South Block, Nottingham University Hospitals NHS Trust Queens Medical Centre
    Nottingham, NG7 2UH, United Kingdom
  • University Hospitals Plymouth NHS Trust-Derriford Hospital-The Lind Research Center, Level 5, Terence Lewis Building
    Plymouth, PL6 8DH, United Kingdom
08

References and documents

Study documents

  • Study protocol · Feb 1, 2021
  • Statistical analysis plan · May 11, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Individual Patient Data (IPD) for this study may be made available upon request via the Clinical Study Data Request site.

Supporting information: Study protocol, Sap, Csr

09

Registry details

Key details

Study ID
NCT03391882
Lead sponsor
Sumitomo Pharma America, Inc.
Responsible party
Sponsor
First posted
Jan 5, 2018
Start date
Dec 19, 2018
Primary completion
Aug 11, 2021
Completion
Aug 11, 2021
Results posted
Dec 16, 2022
Last update
Dec 16, 2022

Study contacts

CNS Medical Director
study director · Sumitomo Pharma America, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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