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LCIG Olanow

Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study

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Year of Publication: 2014

Authors: Olanow CW, Kieburtz K, Odin P, ..., Antonini A; LCIG Horizon Study Group

Journal: Lancet Neurology

Citation: Lancet Neurol 2014;13(2):141-149

Link: https://doi.org/10.1016/S1474-4422(13)70293-X

PDF: https://www.thelancet.com/action/showPdf...4422(13)70293-X

Clinical Question

Does continuous intrajejunal LCIG infusion reduce OFF time and increase ON time without dyskinesia compared with optimized oral levodopa-carbidopa in advanced PD?

Bottom Line

Continuous 16-hour daily intrajejunal LCIG infusion via PEG-J reduced OFF time by 1.91 hours more than optimized oral levodopa-carbidopa (-4.04 vs -2.14 h; p=0.0015) over 12 weeks in advanced Parkinson's disease, with equivalent increase in ON time without troublesome dyskinesia. Established LCIG as an advanced PD device-aided therapy option for severe motor fluctuations refractory to optimal oral therapy.

        Major Points
        Phase 3 multicenter randomized double-blind double-dummy parallel-group trial (LCIG Horizon Study)
71 advanced PD patients with ≥3 h OFF time/day on optimized oral levodopa
Enrolled at 26 sites across US, Germany, and NZ
Randomized 1:1 to LCIG via PEG-J + placebo oral tablets, OR placebo gel + optimized oral levodopa-carbidopa immediate release
12-week treatment phase with preceding NG-tube titration
Primary endpoint: change from baseline in mean OFF time (measured by 3-day patient diary)
OFF time: LCIG -4.04 h vs oral -2.14 h; treatment difference -1.91 h (95% CI -3.05 to -0.76); p=0.0015
ON time without troublesome dyskinesia: LCIG +3.37 h vs oral +1.51 h; difference +1.86 h; p=0.0059
PDQ-39 summary index improvement favored LCIG (difference -7.0; p=0.0155)
UPDRS Part II (ADLs) and Clinician Global Impression also favored LCIG
66 of 71 completed the 12-week treatment
AEs more common with LCIG: procedural pain (38% vs 0%), abdominal pain (31% vs 9%), wound complications, device infections, peritonitis
No deaths related to study treatment
Supported FDA approval of LCIG (Duodopa) for advanced PD with motor fluctuations in 2015

      

Design

Study Type: Phase 3 multicenter randomized double-blind double-dummy parallel-group trial

Randomization: 1

Blinding: Double-blind, double-dummy (each arm received both active and placebo forms)

Follow-up Duration: 12 weeks double-blind

Centers: 26

Countries: USA, Germany, New Zealand

Sample Size: 71

Analyzed: 71

Analysis: Modified intention-to-treat

Inclusion Criteria

Advanced PD
At least 3 hours of OFF time per day
Hoehn-Yahr 3-4 in OFF state
Responsive to levodopa
Optimized on oral levodopa-carbidopa

Exclusion Criteria

Prior DBS
Atypical parkinsonism
Contraindication to PEG-J
Active peptic ulcer
Cognitive impairment precluding diary completion

Baseline Characteristics

Characteristic	Control	Active
N	34	37
Mean age	~65	~65
Hoehn-Yahr	3-4 OFF	3-4 OFF
Baseline OFF time	~6.5 h/d	~6.5 h/d

Arms

Field	Control	LCIG intrajejunal + placebo oral
N	34	37
Intervention	Optimized oral levodopa-carbidopa immediate release + placebo intestinal gel via PEG-J	Continuous LCIG via PEG-J 16 h/day + placebo oral tablets
Duration	12 weeks	12 weeks

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Change from baseline in mean daily OFF time at week 12 (3-day patient diary)	Primary	-2.14 h	-4.04 h		p=0.0015
Change in ON time without troublesome dyskinesia at week 12	Secondary	+1.51 h	+3.37 h	Difference +1.86 h (95% CI 0.56-3.17)	p=0.0059
PDQ-39 summary index improvement	Secondary	Modest improvement	Greater improvement	Difference -7.0 points	p=0.0155
UPDRS Part II (ADLs)	Secondary	Modest improvement	Greater improvement		Favorable
Clinician Global Impression of Change	Secondary	Favorable	More favorable		Favorable for LCIG
Change in ON time with troublesome dyskinesia	Secondary	Minimal change	Minimal change		No worsening of dyskinesia
Procedural pain (PEG-J placement)	Adverse	0%	38%		Higher with LCIG (expected)
Abdominal pain	Adverse	9%	31%		Higher with LCIG
Stoma or wound complications	Adverse	0%	Common (device-related)		LCIG-specific
Nausea	Adverse	6%	14%		Modest imbalance
Dyskinesia	Adverse	9%	6%		Not worse with LCIG
Device malfunction	Adverse	N/A	Common, requiring intervention		LCIG-specific
Serious AEs	Adverse	Uncommon	Higher (device-related)		More in LCIG arm
Serious peritonitis	Adverse	N/A	Rare but reported		Device-specific

Subgroup Analysis

Benefit consistent across age and disease duration subgroups. No differential effect by baseline dyskinesia severity. The LCIG-specific procedural and device complications were the major limiting factor, not a lack of motor efficacy — LCIG's place in therapy is therefore defined by patient willingness to accept PEG-J and associated AEs.

Criticisms

Short 12-week follow-up does not assess long-term device complications and drug tolerability
Small sample size (N=71) — limited power for safety subgroup comparisons
Patients with prior DBS excluded — comparison to DBS not addressed (later studies)
Device-related AEs and procedural burden may not translate across all PD practices
No cost-effectiveness analysis
Long-term effect on cognitive outcomes, gait/falls, and neuropsychiatric symptoms not assessed

Funding

AbbVie (manufacturer of LCIG/Duodopa)

Based on: LCIG Olanow (Lancet Neurology, 2014)

Authors: Olanow CW, Kieburtz K, Odin P, ..., Antonini A; LCIG Horizon Study Group

Citation: Lancet Neurol 2014;13(2):141-149

Content summarized and formatted by NeuroTrials.ai.

LCIG Olanow

(2014)

Objective

Continuous intrajejunal LCIG (levodopa-carbidopa intestinal gel) infusion via PEG-J — to evaluate motor fluctuations vs optimized oral levodopa-carbidopa in advanced Parkinson's disease.

Study Summary

• LCIG reduced OFF time by 1.91 hours more than oral levodopa-carbidopa in advanced PD with severe motor fluctuations.
• Mean reduction in OFF time: -4.04 h (LCIG) vs -2.14 h (oral); treatment difference -1.91 h (95% CI -3.05 to -0.76; p=0.0015).
• ON time without troublesome dyskinesia increased by 1.86 h with LCIG vs 0.85 h with oral (treatment difference +1.86 h; p=0.0059).
• PEG-J tube placement required; procedure-related AEs (abdominal pain, infection) were common.
• No significant change in dyskinesia severity — improved fluctuations without worsening dyskinesia.
• Established LCIG as an advanced-therapy option for PD with motor fluctuations refractory to optimal oral regimens.

Intervention

Continuous intrajejunal LCIG infusion via PEG-J (16 h daily) titrated to optimal dose, vs optimized oral immediate-release levodopa-carbidopa plus placebo gel. Double-blind, double-dummy: patients received either active LCIG + placebo oral, or placebo gel + active oral, for 12 weeks.

Inclusion Criteria

Adults with advanced Parkinson's disease on optimal oral levodopa with ≥3 hours/day OFF time, Hoehn-Yahr 3-4 in OFF state, responsive to levodopa.

Study Design

Arms: LCIG intrajejunal + placebo oral vs Placebo gel + optimized oral levodopa-carbidopa

Patients per Arm: LCIG: 37; Optimized oral: 34 (randomized N=71, 66 completed)

Outcome

• Primary: Change in OFF time at week 12: LCIG -4.04 h vs oral -2.14 h; treatment difference -1.91 h (95% CI -3.05 to -0.76); p=0.0015
• Key secondary: Change in ON time without troublesome dyskinesia: +3.37 h (LCIG) vs +1.51 h (oral); difference +1.86 h (95% CI +0.56 to +3.17); p=0.0059
• PDQ-39 summary index, UPDRS II, CGI all favored LCIG
• AEs more common with LCIG: abdominal pain (31% vs 9%), procedural pain (38% vs 0%), PEG-J complications, infections
• Serious AEs: higher in LCIG (mostly device-related)

Clinical Question

Does continuous intrajejunal LCIG reduce motor fluctuations vs optimized oral levodopa-carbidopa in advanced PD?

Bottom Line

Major Points

Phase 3 multicenter randomized double-blind double-dummy parallel-group trial (LCIG Horizon Study)
71 advanced PD patients with ≥3 h OFF time/day on optimized oral levodopa
Enrolled at 26 sites across US, Germany, and NZ
Randomized 1:1 to LCIG via PEG-J + placebo oral tablets, OR placebo gel + optimized oral levodopa-carbidopa immediate release
12-week treatment phase with preceding NG-tube titration
Primary endpoint: change from baseline in mean OFF time (measured by 3-day patient diary)
OFF time: LCIG -4.04 h vs oral -2.14 h; treatment difference -1.91 h (95% CI -3.05 to -0.76); p=0.0015
ON time without troublesome dyskinesia: LCIG +3.37 h vs oral +1.51 h; difference +1.86 h; p=0.0059
PDQ-39 summary index improvement favored LCIG (difference -7.0; p=0.0155)
UPDRS Part II (ADLs) and Clinician Global Impression also favored LCIG
66 of 71 completed the 12-week treatment
AEs more common with LCIG: procedural pain (38% vs 0%), abdominal pain (31% vs 9%), wound complications, device infections, peritonitis
No deaths related to study treatment
Supported FDA approval of LCIG (Duodopa) for advanced PD with motor fluctuations in 2015

Study Design

Study Type: Phase 3 multicenter randomized double-blind double-dummy parallel-group trial
Randomization: Yes
Blinding: Double-blind, double-dummy (each arm received both active and placebo forms)
Sample Size: 71
Follow-up: 12 weeks double-blind
Centers: 26
Countries: USA, Germany, New Zealand

Primary Outcome

Definition: Change from baseline in mean daily OFF time at week 12 (3-day patient diary)

Control	Intervention	HR/OR	P-value
-2.14 h	-4.04 h	- (-3.05 to -0.76)	p=0.0015

Limitations & Criticisms

Short 12-week follow-up does not assess long-term device complications and drug tolerability
Small sample size (N=71) — limited power for safety subgroup comparisons
Patients with prior DBS excluded — comparison to DBS not addressed (later studies)
Device-related AEs and procedural burden may not translate across all PD practices
No cost-effectiveness analysis
Long-term effect on cognitive outcomes, gait/falls, and neuropsychiatric symptoms not assessed

Citation

Lancet Neurol 2014;13(2):141-149

View Original Publication →

LCIG Olanow

Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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