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
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.
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
If female and of childbearing potential, must agree to use one of the following methods of birth control:
Exclusion Criteria:
APL-130277, sublingual thin film, once daily
Drug: APL-130277
Subcutaneous APO-go, once daily
Drug: APO-go
Subcutaneous APOKYN, once daily
Drug: Apokyn
APL-130277 sublingual thin film
Also known as: amomorphine
Subcutaneous APO-go
Also known as: amomorphine
Subcutaneous APOKYN
Also known as: amomorphine
Maximum Observed Plasma Concentration (Cmax)
Dose normalized maximum observed plasma concentration (Cmax)
Time frame: Day 1
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
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
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
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
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
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
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
Terminal-phase Half-life (t½)
Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.
Time frame: Day 1
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
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
| Milestone | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 |
|---|---|---|---|---|---|---|
| Started | 1 | 1 | 2 | 1 | 1 | 2 |
| Completed | 1 | 1 | 2 | 1 | 1 | 2 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 |
|---|---|---|---|---|---|---|
| Started | 1 | 1 | 2 | 1 | 1 | 2 |
| Completed | 1 | 1 | 2 | 1 | 1 | 2 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 |
|---|---|---|---|---|---|---|
| Started | 1 | 1 | 2 | 1 | 1 | 2 |
| Completed | 1 | 1 | 2 | 1 | 1 | 2 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 |
|---|---|---|---|---|---|---|
| Started | 1 | 1 | 2 | 1 | 1 | 2 |
| Completed | 1 | 0 | 2 | 1 | 1 | 2 |
| Not completed | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 1 | 0 | 0 | 0 | 0 |
| Milestone | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 |
|---|---|---|---|---|---|---|
| Started | 1 | 0 | 2 | 1 | 1 | 2 |
| Completed | 1 | 0 | 2 | 1 | 1 | 2 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 |
Dose normalized maximum observed plasma concentration (Cmax)
| (ng/mL)/(mg) | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous 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) |
Time from dosing to Cmax, observed by inspection of individual subject plots of plasma concentration versus time.
| hour | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| APL 20 mg, APOKYN 3 mg, and APO-go 3 mg | 0.75 (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 mg | 0.63 (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 mg | 0.75 (0.50 to 1.00) | 0.38 (0.25 to 0.50) | 0.25 (0.25 to 0.50) |
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.
| (hxng/mL)/(mg) | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous 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) |
area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule.
| (hxng/mL)/(mg) | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous 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) |
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.
| h | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| APL 20 mg, APOKYN 3 mg, and APO-go 3 mg | 1.69 ± 5.2 | 1.44 ± 4.3 | 1.21 ± 19.3 |
| APL 25 mg, APOKYN 4 mg, and APO-go 4 mg | 1.83 ± 41.5 | 1.70 ± 13.8 | 1.51 ± 19.0 |
| APL 30 mg, APOKYN 5 mg, and APO-go 5 mg | 2.15 ± 15.9 | 1.23 ± 3.4 | 1.08 ± 35.4 |
Metabolite (apomorphine sulfate) to Parent exposure ratio, Cmax, corrected for molecular weight differences.
| no unit | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| APL 20 mg, APOKYN 3 mg and APO-go 3 mg | 61.6 ± 28.8 | 15.2 ± 48.9 | 11.5 ± 4.0 |
| APL 25 mg, APOKYN 4 mg and APO-go 4 mg | 32.0 ± 157.1 | 9.0 ± 149.3 | 7.1 ± 240.3 |
| APL 30 mg, APOKYN 5 mg and APO-go 5 mg | 61.2 ± 87.0 | 13.7 ± 8.2 | 11.3 ± 47.6 |
Apparent total clearance of the drug from plasma extravascular administration, calculated as Dose/AUCinf.
| L/h | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| APL 20 mg, APOKYN 3 mg and APO-go 3 mg | 2766.9 ± 52.4 | 407.9 ± 33.3 | 375.6 ± 32.2 |
| APL 25 mg, APOKYN 4 mg and APO-go 4 mg | 1097.8 ± 99.5 | 250.2 ± 140.6 | 253.7 ± 169.6 |
| APL 30 mg, APOKYN 5 mg and APO-go 5 mg | 1952.1 ± 44.3 | 350.6 ± 4.0 | 299.2 ± 41.0 |
Apparent volume of distribution after extravascular administration, calculated as Dose/(AUCinf \* λz).
| L | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| APL 20 mg, APOKYN 3 mg and APO-go 3 mg | 4440.2 ± 72.0 | 577.5 ± 44.3 | 469.3 ± 19.1 |
| APL 25 mg, APOKYN 4 mg and APO-go 4 mg | 1733.4 ± 52.8 | 420.8 ± 193.7 | 372.2 ± 231.1 |
| APL 30 mg, APOKYN 5 mg and APO-go 5 mg | 3419.5 ± 67.4 | 452.0 ± 14.7 | 324.2 ± 73.7 |
Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.
| h | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| APL 20 mg, APOKYN 3 mg and APO-go 3 mg | 1.11 ± 15.6 | 0.98 ± 9.9 | 0.87 ± 12.6 |
| APL 25 mg, APOKYN 4 mg and APO-go 4 mg | 1.09 ± 34.3 | 1.17 ± 20.6 | 1.02 ± 19.7 |
| APL 30 mg, APOKYN 5 mg and APO-go 5 mg | 1.21 ± 20.5 | 0.89 ± 18.7 | 0.75 ± 35.5 |
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.
| /h | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| APL 20 mg, APOKYN 3 mg and APO-go 3 mg | 0.62 ± 15.6 | 0.71 ± 9.9 | 0.80 ± 12.6 |
| APL 25 mg, APOKYN 4 mg and APO-go 4 mg | 0.63 ± 34.3 | 0.59 ± 20.6 | 0.68 ± 19.7 |
| APL 30 mg, APOKYN 5 mg and APO-go 5 mg | 0.57 ± 20.5 | 0.78 ± 18.7 | 0.92 ± 35.5 |
Metabolite (apomorphine sulfate) to Parent exposure ratio, AUClast, corrected for molecular weight differences.
| no unit | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| APL 20 mg, APOKYN 3 mg and APO-go 3 mg | 98.16 ± 6.4 | 36.22 ± 3.0 | 32.19 ± 9.9 |
| APL 25 mg, APOKYN 4 mg and APO-go 4 mg | 45.79 ± 169.9 | 18.70 ± 162.8 | 16.27 ± 221.6 |
| APL 30 mg, APOKYN 5 mg and APO-go 5 mg | 98.07 ± 55.4 | 33.63 ± 6.2 | 26.22 ± 43.6 |
Collected over 16 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| APL-130277, Sublingual Thin Film | 0/8 (0%) | 1/8 (12.5%) | 1/8 (12.5%) |
| Subcutaneous APOKYN | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) |
| Subcutaneous APO-go | 0/8 (0%) | 0/8 (0%) | 3/8 (37.5%) |
| Event | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| FallInjury, poisoning and procedural complications | 1/8 | 0/7 | 0/8 |
| Rib fractureInjury, poisoning and procedural complications | 1/8 | 0/7 | 0/8 |
| Splenic ruptureInjury, poisoning and procedural complications | 1/8 | 0/7 | 0/8 |
| Event | APL-130277, Sublingual Thin Film | Subcutaneous APOKYN | Subcutaneous APO-go |
|---|---|---|---|
| NauseaGastrointestinal disorders | 1/8 | 1/7 | 2/8 |
| SomnolenceNervous system disorders | 0/8 | 1/7 | 0/8 |
| Injection site bruisingGeneral disorders | 0/8 | 0/7 | 1/8 |
| DyskinesiaNervous system disorders | 0/8 | 0/7 | 1/8 |
| HyperhidrosisSkin and subcutaneous tissue disorders | 0/8 | 0/7 | 1/8 |
| Age, Categorical(Participants) | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 | Total |
|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | 1 | 1 | 0 | 0 | 1 | 3 |
| >=65 years | 1 | 0 | 1 | 1 | 1 | 1 | 5 |
| Age, Continuous(Years) | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 | Total |
|---|---|---|---|---|---|---|---|
| Mean | 75 | 51 | 67.5 ± 9.19 | 67 | 73 | 68.5 ± 9.19 | 67.3 ± 8.7 |
| Sex: Female, Male(Participants) | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 | Total |
|---|---|---|---|---|---|---|---|
| Female | 0 | 1 | 0 | 0 | 0 | 1 | 2 |
| Male | 1 | 0 | 2 | 1 | 1 | 1 | 6 |
| Ethnicity (NIH/OMB)(Participants) | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 1 | 1 | 2 | 1 | 1 | 2 | 8 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 1 | 1 | 2 | 1 | 1 | 2 | 8 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Country(Participants) | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 | Total |
|---|---|---|---|---|---|---|---|
| United States | 1 | 1 | 2 | 1 | 1 | 2 | 8 |
| Height (cm) at Baseline(cm) | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 | Total |
|---|---|---|---|---|---|---|---|
| Mean | 172.7 | 157.5 | 174.95 ± 11.243 | 175.3 | 177.8 | 171.25 ± 19.445 | 171.96 ± 10.545 |
| Body Weight (kg) at Baseline(kg) | APL-130277, Then APOKYN, Then APO-go | APL-130277, Then APO-go, Then APOKYN | APOKYN, Then APL-130277, Then APO-go | APOKYN, Then APO-go, Then APL-130277 | APO-go, Then APL-130277, Then APOKYN | APO-go, Then APOKYN, Then APL-130277 | Total |
|---|---|---|---|---|---|---|---|
| Mean | 86.3 | 59.4 | 86.7 ± 20.506 | 73 | 84.4 | 71.2 ± 25.032 | 77.36 ± 15.895 |
5 further baseline measures are reported on the registry.
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Sumitomo Pharma America, Inc.