Trial Outcomes & Findings for A Study to Compare Plasma Levels of Levodopa, Carbidopa and Entacapone After TRIGEL or Duodopa Infusion in PD Patients (NCT NCT02448914)

NCT ID: NCT02448914

Last Updated: 2016-05-23

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 11 participants
• Primary outcome timeframe: During 14 h infusion on 2 consecutive days
• Results posted on: 2016-05-23

Participant Flow

Participant milestones

Measure	TRIGEL First, Then Duodopa First Intervention (Day 1): TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). Second Intervention (Day 2): Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made. All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.	Duodopa First, Then TRIGEL First Intervention (Day 1): Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). Second Intervention (Day 2): TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made. All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.
First Intervention (1 Day) STARTED	6	5
First Intervention (1 Day) COMPLETED	6	5
First Intervention (1 Day) NOT COMPLETED	0	0
Second Intervention (1 Day) STARTED	6	5
Second Intervention (1 Day) COMPLETED	6	5
Second Intervention (1 Day) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Compare Plasma Levels of Levodopa, Carbidopa and Entacapone After TRIGEL or Duodopa Infusion in PD Patients

Baseline characteristics by cohort

Measure	TRIGEL and Duodopa in Randomized Order n=11 Participants TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made. All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Age, Continuous	69.5 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Region of Enrollment Sweden	11 participants n=5 Participants

PRIMARY outcome

Timeframe: During 14 h infusion on 2 consecutive days

Outcome measures

Measure	TRIGEL n=11 Participants TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made.	Duodopa n=11 Participants Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.
Dose Adjusted Area Under the Curve (AUC) (0-14h) for Levodopa	40.6 h*ng/mL/mg Interval 22.3 to 69.4	29.4 h*ng/mL/mg Interval 21.7 to 52.8

SECONDARY outcome

Timeframe: During 3-14h infusion on 2 consecutive days

The individual patient's coefficient of variation (CV) of levodopa plasma concentration during administration of TRIGEL and Duodopa respectively between 3 and 14 h after start of study drug. CV=100*sqrt (exp (SDlog*SDlog)-1) were SDlog denotes the standard deviation computed on logged plasma concentrations.

Outcome measures

Measure	TRIGEL n=11 Participants TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made.	Duodopa n=11 Participants Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.
Intra-individual Coefficient of Variation (3-14h) for Levodopa	13.8 percentage of variability Interval 6.5 to 36.7	10.6 percentage of variability Interval 6.1 to 19.2

SECONDARY outcome

Timeframe: During 14 h infusion on 2 consecutive days

Outcome measures

Measure	TRIGEL n=11 Participants TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made.	Duodopa n=11 Participants Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.
Dose Adjusted AUC (0-14h) for Carbidopa	22.1 h*ng/mL/mg Interval 13.6 to 52.5	18.8 h*ng/mL/mg Interval 11.5 to 37.9

SECONDARY outcome

Timeframe: Patients will be followed for the duration of the hospital stay, an expected average of 3 days

Outcome measures

Measure	TRIGEL n=11 Participants TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made.	Duodopa n=11 Participants Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.
Number of Adverse Events	10 adverse events	6 adverse events

SECONDARY outcome

Timeframe: During 14 h infusion on 2 consecutive days

Outcome measures

Measure	TRIGEL n=11 Participants TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made.	Duodopa n=11 Participants Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.
Dose Adjusted AUC (0-14h) for 3-O-Methyldopa	155 h*ng/mL/mg Interval 83.9 to 258.3	131 h*ng/mL/mg Interval 72.1 to 182.2

OTHER_PRE_SPECIFIED outcome

Timeframe: TRS assessments were made every 30 minutes from start of study drug administration until 3 h, every hour between 3 and 14 h and every 30 minutes between 14 and 17 h.

Dyskinesia and parkinsonism symptoms were evaluated throughout the study period as an assessment of the clinical response. To assess the ON/OFF effect the Treatment Response Scale (TRS) was used. The TRS ranges from -3 (severe "OFF") to +3 ("ON" with severe dyskinesia). Results from the TRS recordings are presented as the mean percentage of time patients were in functional ON state (TRS: -1 to +1) during the time interval 3-14 h.

Outcome measures

Measure	TRIGEL n=11 Participants TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made.	Duodopa n=11 Participants Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.
Treatment Response Scale (ON/OFF Effect) - Mean % of Time Patients Were in Functional ON State During 3-14 h	91.7 Mean % of time Interval 18.3 to 100.0	91.0 Mean % of time Interval 0.758 to 100.0

Adverse Events

TRIGEL

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Duodopa

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	TRIGEL n=11 participants at risk TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). The TRIGEL doses corresponded to 80% of the pre-study individually optimized doses of Duodopa in the first cohort of 5 patients. After the first cohort, a pre-planned interim analysis was performed. It was decided that the morning dose would be adjusted from 80% to 90% of the corresponding Duodopa dose for the second cohort. No other changes to the dosage regimens were made.	Duodopa n=11 participants at risk Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). All patients received TRIGEL and Duodopa treatment on two consecutive days in the study. Both TRIGEL and Duodopa were administered during 14 h in total. Each treatment consisted of three individually adjusted and pre-defined doses: a morning dose, a continuous administration, and extra doses (if required). All Duodopa doses corresponded to 100% of the pre-study individually optimized doses of Duodopa.
Gastrointestinal disorders Diarrhoea	0.00% 0/11	9.1% 1/11 • Number of events 1
Gastrointestinal disorders Nausea	9.1% 1/11 • Number of events 1	9.1% 1/11 • Number of events 2
Injury, poisoning and procedural complications Injection site haematoma	9.1% 1/11 • Number of events 3	9.1% 1/11 • Number of events 1
Injury, poisoning and procedural complications Laceration	9.1% 1/11 • Number of events 1	0.00% 0/11
Nervous system disorders Dizziness	18.2% 2/11 • Number of events 2	0.00% 0/11
Nervous system disorders Headache	27.3% 3/11 • Number of events 3	9.1% 1/11 • Number of events 1
Skin and subcutaneous tissue disorders Cold sweat	0.00% 0/11	9.1% 1/11 • Number of events 1

Additional Information

Roger Bolsöy, CEO

LobSor Pharmaceutical AB

Phone: +46 (0) 72 222 44 08

Email: roger.bolsoy@lsmgroup.se

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER