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CompletedNCT03292016Updated Aug 13, 2020Results posted

A Study That Compares the Extent to Which Apomorphine Becomes Available in the Body After Taking Either an Investigational Drug Containing Apomorphine or Apomorphine That is Injected Under the Skin in People With PD Complicated by "OFF" Episodes

A Phase 2 interventional study of APL-130277 and APO-go in Parkinson Disease, sponsored by Sumitomo Pharma America, Inc.. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-08-13.

Sponsored by Sumitomo Pharma America, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
8
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

A study that compares the extent to which apomorphine becomes available in the body after taking either an investigational drug containing apomorphine or apomorphine that is injected under the skin in people with PD complicated by "OFF" episodes.

Read the detailed description

This multi-center study will aim to evaluate the pharmacokinetics (PK) and comparative bioavailability of a single dose of APL-130277 sublingual thin film with subcutaneous (s.c.) APO-go® and s.c. APOKYN® in subjects with Parkinson's disease (PD). The dose of APOKYN® (≤ 5 mg) will be based on the subjects' current prescribed dose. The study is designed as an open-label, randomized, three-way crossover. Subjects will receive all three treatment arms with a minimum 1-day wash-out between each visit (excluding the screening visit) and will be randomly assigned to one of the six sequences

02

Conditions studied

  • Parkinson Disease

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Keywords

  • Off Episodes
  • Parkinson Disease
03

Who can participate

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

Inclusion criteria

  1. Male or female ≥ 18 years of age.
  2. Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
  3. Clinically meaningful response to Levodopa (L-Dopa) with well-defined "OFF" episodes, as determined by the Investigator.
  4. Receiving APOKYN® of ≤ 5 mg per dose for at least 4 weeks before the Screening Visit.
  5. Receiving stable doses of L-Dopa/carbidopa (immediate or sustained release) administered at least 4 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the Screening Visit. Adjunctive PD medication regimens must be maintained at a stable dose for at least 4 weeks prior to the Screening Visit with the exception that MAOB inhibitors must be maintained at a stable level for at least 8 weeks prior to the Screening Visit.
  6. No planned medication change(s) or surgical intervention anticipated during the course of study.
  7. Patients must experience a well-defined "OFF" episode in the morning if they do not take their morning PD medications on schedule, and must be willing to delay morning doses on the 3 study dosing days
  8. Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
  9. Mini-Mental State Examination (MMSE) score > 23.
  10. If female and of childbearing potential, must agree to use one of the following methods of birth control:

    • Oral contraceptive;
    • Contraceptive patch;
    • Barrier (diaphragm, sponge or condom) plus spermicidal preparations;
    • Intrauterine contraceptive system;
    • Levonorgestrel implant;
    • Medroxyprogesterone acetate contraceptive injection;
    • Complete abstinence from sexual intercourse;
    • Hormonal vaginal contraceptive ring; or
    • Surgical sterilization or partner sterile (must have documented proof).
  11. Male patients must be either surgically sterile, agree to be sexually abstinent or use a barrier method of birth control (e.g., condom) or maintain a monogamous relationship with a person who is not of child-bearing potential from first study drug administration until 30days after final drug administration.
  12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study.
  13. Able to understand the consent form, and to provide written informed consent

Exclusion criteria

Exclusion Criteria:

  1. Atypical or secondary parkinsonism.
  2. Previous treatment with any of the following: continuous subcutaneous (s.c.) apomorphine infusion; or Duodopa/Duopa.
  3. Contraindications to APO-go® or APOKYN® or hypersensitivity to apomorphine hydrochloride or any marcrolide antibiotic or any of the ingredients APO-go® or APOKYN® (notably sodium metabisulfite).
  4. Female who is pregnant or lactating.
  5. Participation in a clinical trial within 30 days prior to the Screening Visit.
  6. Receipt of any investigational (ie, unapproved) medication within 30 days prior to the Screening Visit.
  7. Any selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine and clozapine) or dopamine depleting agents within 30 days prior to the Screening Visit.
  8. Drug or alcohol dependency in the past 12 months.
  9. History of malignant melanoma.
  10. Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.
  11. Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
  12. History of clinically significant hallucinations during the past 6 months.
  13. History of clinically significant impulse control disorder(s).
  14. Dementia that precludes providing informed consent or would interfere with participation in the study.
  15. Current suicidal ideation within one year prior to the Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.
  16. Donation of blood plasma in the 30 days prior to first dosing.
  17. Cankers or mouth sores within 30 days prior to the Screening Visit, 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 patient into the study.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
8 participants (actual)

Study arms

  • Experimental
    APL-130277, sublingual thin film

    APL-130277, sublingual thin film, once daily

    Drug: APL-130277

  • Active comparator
    Subcutaneous APO-go

    Subcutaneous APO-go, once daily

    Drug: APO-go

  • Active comparator
    Subcutaneous APOKYN

    Subcutaneous APOKYN, once daily

    Drug: Apokyn

Interventions

  • DrugAPL-130277

    APL-130277 sublingual thin film

    Also known as: amomorphine

  • DrugAPO-go

    Subcutaneous APO-go

    Also known as: amomorphine

  • DrugApokyn

    Subcutaneous APOKYN

    Also known as: amomorphine

05

What researchers measure

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax)

    Dose normalized maximum observed plasma concentration (Cmax)

    Time frame: Day 1

  2. Observed Time of the Maximum Concentration (Tmax)

    Time from dosing to Cmax, observed by inspection of individual subject plots of plasma concentration versus time.

    Time frame: Day 1

  3. Area Under the Concentration- Time Curve (AUC Last)

    area under the concentration-time curve from time zero to the last measurable plasma concentration-time curve using the linear up log down trapezoidal rule.

    Time frame: Day 1

  4. Area Under the Concentration- Time Curve (AUC Inf)

    area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule.

    Time frame: Day 1

  5. Mean Residence Time (MRT)

    Mean residence time during one dosing interval calculated using the following equation: MRT = AUMCinf/AUC inf. AUMCinf is the area under the first moment (time.plasma concentration vs. time) curve.

    Time frame: Day 1

  6. Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax

    Metabolite (apomorphine sulfate) to Parent exposure ratio, Cmax, corrected for molecular weight differences.

    Time frame: Day 1

  7. Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)

    Apparent total clearance of the drug from plasma extravascular administration, calculated as Dose/AUCinf.

    Time frame: Day 1

  8. Apparent Volume of Distribution After Non-intravenous Administration (V/F)

    Apparent volume of distribution after extravascular administration, calculated as Dose/(AUCinf \* λz).

    Time frame: Day 1

  9. Terminal-phase Half-life (t½)

    Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.

    Time frame: Day 1

  10. Terminal-phase Rate Constant ( λz)

    Apparent terminal elimination rate constant, determined by log linear regression of the plasma concentration versus time data that was judged to be in the log-linear elimination phase. At least 3 data points in the terminal phase will be used in the determination of the rate constant.

    Time frame: Day 1

  11. Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last

    Metabolite (apomorphine sulfate) to Parent exposure ratio, AUClast, corrected for molecular weight differences.

    Time frame: Day 1

06

Results

Posted Aug 13, 2020

Participant flow

First Intervention
Participant flow — First Intervention
MilestoneAPL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277
Started112112
Completed112112
Not completed000000
First Washout
Participant flow — First Washout
MilestoneAPL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277
Started112112
Completed112112
Not completed000000
Second Intervention
Participant flow — Second Intervention
MilestoneAPL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277
Started112112
Completed112112
Not completed000000
Second Washout
Participant flow — Second Washout
MilestoneAPL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277
Started112112
Completed102112
Not completed010000
Withdrew: Adverse event010000
Third Intervention
Participant flow — Third Intervention
MilestoneAPL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277
Started102112
Completed102112
Not completed000000

Outcome measures

PrimaryMaximum Observed Plasma Concentration (Cmax)

Dose normalized maximum observed plasma concentration (Cmax)

Time frame:
Day 1
Reported as:
Geometric least squares mean · (ng/mL)/(mg)
Maximum Observed Plasma Concentration (Cmax)
(ng/mL)/(mg)APL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
Maximum Observed Plasma Concentration (Cmax)0.281 (0.191 to 0.413)2.29 (1.46 to 3.59)2.74 (1.82 to 4.13)
Statistical analysis
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Mixed Models Analysis · Geometric mean ratio (apl-130277/apokyn): 12.3 · 90% CI 7.5 to 20.3With fixed effects-treatment and period, random effect-subject nested within sequence to analyze natural-log transformed dose normalized parameter.
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Geometric mean ratio (apl-130277/apo-go): 10.3 · 90% CI 6.5 to 16.3
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Geometric mean ratio (apokyn/apo-go): 83.4 · 90% CI 50.5 to 137.6
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Ratio: 0.21The comparative bioavailability calculated as the ratio of the Test/Reference between APL 20 mg and APO-Go 3 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Ratio: 0.13The comparative bioavailability calculated as the ratio of the Test/Reference between APL 20 mg and APOKYN 3 mg
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Ratio: 1.16The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 3 mg and APOKYN 3 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Ratio: 0.16The comparative bioavailability calculated as the ratio of the Test/Reference between APL 25 mg and APO-Go 4 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Ratio: 0.17The comparative bioavailability calculated as the ratio of the Test/Reference between APL 25 mg and APOKYN 4 mg
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Ratio: 1.12The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 4 mg and APOKYN 4 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Ratio: 0.08The comparative bioavailability calculated as the ratio of the Test/Reference between APL 30 mg and APO-Go 5 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Ratio: 0.09The comparative bioavailability calculated as the ratio of the Test/Reference between APL 30 mg and APOKYN 5 mg
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Ratio: 1.04The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 5 mg and APOKYN 5 mg
PrimaryObserved Time of the Maximum Concentration (Tmax)

Time from dosing to Cmax, observed by inspection of individual subject plots of plasma concentration versus time.

Time frame:
Day 1
Reported as:
Median · hour
Observed Time of the Maximum Concentration (Tmax)
hourAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
APL 20 mg, APOKYN 3 mg, and APO-go 3 mg0.75 (0.52 to 0.75)0.38 (0.25 to 0.50)0.38 (0.25 to 0.50)
APL 25 mg, APOKYN 4 mg, and APO-go 4 mg0.63 (0.25 to 1.02)0.25 (0.25 to 0.25)0.26 (0.25 to 0.27)
APL 30 mg, APOKYN 5 mg, and APO-go 5 mg0.75 (0.50 to 1.00)0.38 (0.25 to 0.50)0.25 (0.25 to 0.50)
Statistical analysis
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Sign test · p = 0.0625
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Sign test · p = 0.0313
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Sign test · p = >0.9999
PrimaryArea Under the Concentration- Time Curve (AUC Last)

area under the concentration-time curve from time zero to the last measurable plasma concentration-time curve using the linear up log down trapezoidal rule.

Time frame:
Day 1
Reported as:
Geometric least squares mean · (hxng/mL)/(mg)
Area Under the Concentration- Time Curve (AUC Last)
(hxng/mL)/(mg)APL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
Area Under the Concentration- Time Curve (AUC Last)0.500 (0.344 to 0.726)2.91 (1.97 to 4.30)3.00 (2.05 to 4.39)
Statistical analysis
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Mixed Models Analysis · Geometric mean ratio (apl-130277/apokyn): 17.2 · 90% CI 13.1 to 22.5With fixed effects-treatment and period, random effect-subject nested within sequence to analyze natural-log transformed dose normalized parameter.
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Mixed Models Analysis · Geometric mean ratio (apl-130277/apokyn): 16.7 · 90% CI 13.0 to 21.3
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Geometric mean ratio (apokyn/apo-go): 96.9 · 90% CI 74.2 to 126.4
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Ratio: 0.32The comparative bioavailability calculated as the ratio of the Test/Reference between APL 20 mg and APO-Go 3 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Ratio: 0.16The comparative bioavailability calculated as the ratio of the Test/Reference between APL 20 mg and APOKYN 3 mg
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Ratio: 1.09The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 3 mg and APOKYN 3 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Ratio: 0.23The comparative bioavailability calculated as the ratio of the Test/Reference between APL 25 mg and APO-Go 4 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Ratio: 0.23The comparative bioavailability calculated as the ratio of the Test/Reference between APL 25 mg and APOKYN 4 mg
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Ratio: 1.00The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 4 mg and APOKYN 4 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Ratio: 0.15The comparative bioavailability calculated as the ratio of the Test/Reference between APL 30 mg and APO-Go 5 mg
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Ratio: 0.14The comparative bioavailability calculated as the ratio of the Test/Reference between APL 30 mg and APOKYN 5 mg
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Ratio: 0.96The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 5 mg and APOKYN 5 mg
PrimaryArea Under the Concentration- Time Curve (AUC Inf)

area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule.

Time frame:
Day 1
Reported as:
Geometric least squares mean · (hxng/mL)/(mg)
Area Under the Concentration- Time Curve (AUC Inf)
(hxng/mL)/(mg)APL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
Area Under the Concentration- Time Curve (AUC Inf)0.52 (0.36 to 0.76)2.97 (2.01 to 4.39)3.04 (2.08 to 4.45)
Statistical analysis
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Mixed Models Analysis · Geometric mean ratio (apl-130277/apokyn): 17.6 · 90% CI 13.7 to 22.5With fixed effects-treatment and period, random effect-subject nested within sequence to analyze natural-log transformed dose normalized parameter.
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Mixed Models Analysis · Geometric mean ratio (apl-130277/apo-go): 17.2 · 90% CI 13.7 to 21.6
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Mixed Models Analysis · Geometric mean ratio (apokyn/apo-go): 97.8 · 90% CI 76.6 to 124.8
PrimaryMean Residence Time (MRT)

Mean residence time during one dosing interval calculated using the following equation: MRT = AUMCinf/AUC inf. AUMCinf is the area under the first moment (time.plasma concentration vs. time) curve.

Time frame:
Day 1
Reported as:
Geometric mean · h
Mean Residence Time (MRT)
hAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
APL 20 mg, APOKYN 3 mg, and APO-go 3 mg1.69 ± 5.21.44 ± 4.31.21 ± 19.3
APL 25 mg, APOKYN 4 mg, and APO-go 4 mg1.83 ± 41.51.70 ± 13.81.51 ± 19.0
APL 30 mg, APOKYN 5 mg, and APO-go 5 mg2.15 ± 15.91.23 ± 3.41.08 ± 35.4
PrimaryMetabolite/Parent (M/P) Drug Concentration Ratio -Cmax

Metabolite (apomorphine sulfate) to Parent exposure ratio, Cmax, corrected for molecular weight differences.

Time frame:
Day 1
Reported as:
Geometric mean · no unit
Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax
no unitAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
APL 20 mg, APOKYN 3 mg and APO-go 3 mg61.6 ± 28.815.2 ± 48.911.5 ± 4.0
APL 25 mg, APOKYN 4 mg and APO-go 4 mg32.0 ± 157.19.0 ± 149.37.1 ± 240.3
APL 30 mg, APOKYN 5 mg and APO-go 5 mg61.2 ± 87.013.7 ± 8.211.3 ± 47.6
PrimaryApparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)

Apparent total clearance of the drug from plasma extravascular administration, calculated as Dose/AUCinf.

Time frame:
Day 1
Reported as:
Geometric mean · L/h
Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)
L/hAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
APL 20 mg, APOKYN 3 mg and APO-go 3 mg2766.9 ± 52.4407.9 ± 33.3375.6 ± 32.2
APL 25 mg, APOKYN 4 mg and APO-go 4 mg1097.8 ± 99.5250.2 ± 140.6253.7 ± 169.6
APL 30 mg, APOKYN 5 mg and APO-go 5 mg1952.1 ± 44.3350.6 ± 4.0299.2 ± 41.0
PrimaryApparent Volume of Distribution After Non-intravenous Administration (V/F)

Apparent volume of distribution after extravascular administration, calculated as Dose/(AUCinf \* λz).

Time frame:
Day 1
Reported as:
Geometric mean · L
Apparent Volume of Distribution After Non-intravenous Administration (V/F)
LAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
APL 20 mg, APOKYN 3 mg and APO-go 3 mg4440.2 ± 72.0577.5 ± 44.3469.3 ± 19.1
APL 25 mg, APOKYN 4 mg and APO-go 4 mg1733.4 ± 52.8420.8 ± 193.7372.2 ± 231.1
APL 30 mg, APOKYN 5 mg and APO-go 5 mg3419.5 ± 67.4452.0 ± 14.7324.2 ± 73.7
PrimaryTerminal-phase Half-life (t½)

Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.

Time frame:
Day 1
Reported as:
Geometric mean · h
Terminal-phase Half-life (t½)
hAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
APL 20 mg, APOKYN 3 mg and APO-go 3 mg1.11 ± 15.60.98 ± 9.90.87 ± 12.6
APL 25 mg, APOKYN 4 mg and APO-go 4 mg1.09 ± 34.31.17 ± 20.61.02 ± 19.7
APL 30 mg, APOKYN 5 mg and APO-go 5 mg1.21 ± 20.50.89 ± 18.70.75 ± 35.5
Statistical analysis
  • APL-130277, Sublingual Thin Film vs Subcutaneous APO-go · Wilcoxon (Mann-Whitney) · p = 0.0313
  • APL-130277, Sublingual Thin Film vs Subcutaneous APOKYN · Wilcoxon (Mann-Whitney) · p = 0.0625
  • Subcutaneous APOKYN vs Subcutaneous APO-go · Wilcoxon (Mann-Whitney) · p = >0.9999
PrimaryTerminal-phase Rate Constant ( λz)

Apparent terminal elimination rate constant, determined by log linear regression of the plasma concentration versus time data that was judged to be in the log-linear elimination phase. At least 3 data points in the terminal phase will be used in the determination of the rate constant.

Time frame:
Day 1
Reported as:
Geometric mean · /h
Terminal-phase Rate Constant ( λz)
/hAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
APL 20 mg, APOKYN 3 mg and APO-go 3 mg0.62 ± 15.60.71 ± 9.90.80 ± 12.6
APL 25 mg, APOKYN 4 mg and APO-go 4 mg0.63 ± 34.30.59 ± 20.60.68 ± 19.7
APL 30 mg, APOKYN 5 mg and APO-go 5 mg0.57 ± 20.50.78 ± 18.70.92 ± 35.5
PrimaryMetabolite/Parent (M/P) Drug Concentration Ratio -AUC Last

Metabolite (apomorphine sulfate) to Parent exposure ratio, AUClast, corrected for molecular weight differences.

Time frame:
Day 1
Reported as:
Geometric mean · no unit
Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last
no unitAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
APL 20 mg, APOKYN 3 mg and APO-go 3 mg98.16 ± 6.436.22 ± 3.032.19 ± 9.9
APL 25 mg, APOKYN 4 mg and APO-go 4 mg45.79 ± 169.918.70 ± 162.816.27 ± 221.6
APL 30 mg, APOKYN 5 mg and APO-go 5 mg98.07 ± 55.433.63 ± 6.226.22 ± 43.6

Adverse events

Collected over 16 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
APL-130277, Sublingual Thin Film0/8 (0%)1/8 (12.5%)1/8 (12.5%)
Subcutaneous APOKYN0/7 (0%)0/7 (0%)1/7 (14.3%)
Subcutaneous APO-go0/8 (0%)0/8 (0%)3/8 (37.5%)
Most frequent serious events
Most frequent serious events
EventAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
FallInjury, poisoning and procedural complications1/80/70/8
Rib fractureInjury, poisoning and procedural complications1/80/70/8
Splenic ruptureInjury, poisoning and procedural complications1/80/70/8
Most frequent other events
Most frequent other events
EventAPL-130277, Sublingual Thin FilmSubcutaneous APOKYNSubcutaneous APO-go
NauseaGastrointestinal disorders1/81/72/8
SomnolenceNervous system disorders0/81/70/8
Injection site bruisingGeneral disorders0/80/71/8
DyskinesiaNervous system disorders0/80/71/8
HyperhidrosisSkin and subcutaneous tissue disorders0/80/71/8

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)APL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277Total
<=18 years0000000
Between 18 and 65 years0110013
>=65 years1011115
Age, Continuous
Age, Continuous(Years)APL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277Total
Mean755167.5 ± 9.19677368.5 ± 9.1967.3 ± 8.7
Sex: Female, Male
Sex: Female, Male(Participants)APL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277Total
Female0100012
Male1021116
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)APL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277Total
Hispanic or Latino0000000
Not Hispanic or Latino1121128
Unknown or Not Reported0000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)APL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277Total
American Indian or Alaska Native0000000
Asian0000000
Native Hawaiian or Other Pacific Islander0000000
Black or African American0000000
White1121128
More than one race0000000
Unknown or Not Reported0000000
Country
Country(Participants)APL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277Total
United States1121128
Height (cm) at Baseline
Height (cm) at Baseline(cm)APL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277Total
Mean172.7157.5174.95 ± 11.243175.3177.8171.25 ± 19.445171.96 ± 10.545
Body Weight (kg) at Baseline
Body Weight (kg) at Baseline(kg)APL-130277, Then APOKYN, Then APO-goAPL-130277, Then APO-go, Then APOKYNAPOKYN, Then APL-130277, Then APO-goAPOKYN, Then APO-go, Then APL-130277APO-go, Then APL-130277, Then APOKYNAPO-go, Then APOKYN, Then APL-130277Total
Mean86.359.486.7 ± 20.5067384.471.2 ± 25.03277.36 ± 15.895

5 further baseline measures are reported on the registry.

07

Study locations

3 sites
  • Parkinson's Disease and Movement Disorders Center of Boca Raton
    Boca Raton, Florida 33486, United States
  • Parkinson's Disese Treatment Center of SW Florida
    Port Charlotte, Florida 33980, United States
  • QUEST Research Institute
    Farmington Hills, Michigan 48334, United States
08

References and documents

Publications

  • Agbo F, Isaacson SH, Gil R, Chiu YY, Brantley SJ, Bhargava P, Navia B. Pharmacokinetics and Comparative Bioavailability of Apomorphine Sublingual Film and Subcutaneous Apomorphine Formulations in Patients with Parkinson's Disease and "OFF" Episodes: Results of a Randomized, Three-Way Crossover, Open-Label Study. Neurol Ther. 2021 Dec;10(2):693-709. doi: 10.1007/s40120-021-00251-6. Epub 2021 May 15. PubMed 33991326 ↗

Study documents

  • Study protocol · May 10, 2017
  • Statistical analysis plan · Jan 7, 2019

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

09

Registry details

Key details

Study ID
NCT03292016
Lead sponsor
Sumitomo Pharma America, Inc.
Responsible party
Sponsor
First posted
Sep 25, 2017
Start date
Aug 22, 2017
Primary completion
Mar 5, 2019
Completion
Mar 5, 2019
Results posted
Aug 13, 2020
Last update
Aug 13, 2020

Study contacts

CNS Mecdical Director
study chair · Sunovion Pharmacetuicals 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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