Detailed Outcome Data

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Clinical Review Report: Levodopa/Carbidopa (Duodopa): (Abbvie Corporation): Indication: For the treatment of patients with advanced levodopa-responsive Parkinson’s disease who do not have satisfactory control of severe, debilitating motor fluctuations and hyper-/dyskinesia despite optimized treatment with available combinations of Parkinson’s medicinal products, and, for whom the benefits of this treatment may outweigh the risks associated with the insertion and long-term use of the percutaneous endoscopic gastrostomy-jejunostomy (PEG-J) tube required for administration [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Sep.

Cover of Clinical Review Report: Levodopa/Carbidopa (Duodopa)

Clinical Review Report: Levodopa/Carbidopa (Duodopa): (Abbvie Corporation): Indication: For the treatment of patients with advanced levodopa-responsive Parkinson’s disease who do not have satisfactory control of severe, debilitating motor fluctuations and hyper-/dyskinesia despite optimized treatment with available combinations of Parkinson’s medicinal products, and, for whom the benefits of this treatment may outweigh the risks associated with the insertion and long-term use of the percutaneous endoscopic gastrostomy-jejunostomy (PEG-J) tube required for administration [Internet].

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Appendix 4Detailed Outcome Data

Table 22Summary of “Off” Time Sensitivity Analyses (Full Analysis Set)

End Point	Study 001/002
	Adjusted LS Mean Change From Baseline at Week 12 (SE)
	LCIG + PBO IR OLC Capsules	PBO LCIG + IR OLC Capsules	Adjusted LS MD in Change From Baseline (95% CI)	P value
Off time, hours per day
MMRM for imputed data^a	−4.09 (0.55)	−2.25 (0.56)	−1.84 (−2.98 to −0.70)	0.0021
Off time, hours per day (LOCF)^b
Without covariate of rescue medication on valid PDHD days	−4.02 (0.65)	−2.13 (0.66)	−1.89 (−3.03 to −0.75)	0.0016
With covariate of rescue medication over the treatment period	−4.02 (0.65)	−2.14 (0.66)	−1.88 (−3.03 to −0.73)	0.0018
With values on final PDHD days with rescue medication use replaced by average daily normalized “off” time at baseline	−3.29 (0.70)	−1.47 (0.70)	−1.82 (−3.05 to −0.60)	0.0042
Excluding values on final PDHD days with rescue medication use	−4.30 (0.68)	−2.52 (0.69)	−1.78 (−2.97 to −0.58)	0.0043

: ANCOVA = analysis of covariance; CI = confidence interval; IR = immediate-release; LCIG = levodopa/carbidopa intestinal gel; LOCF = last observation carried forward; LS = least squares; MD = mean difference; MMRM = mixed-effects models for repeated measures; OLC = oral levodopa/carbidopa; PBO = placebo; PDHDD = Parkinson disease home diary; SE = standard error.
: Note: The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 0 to 16-hour scale (i.e., 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis.
a: LS means, SE, CI, and P values are based on a repeated measures linear regression model of the change from baseline score, with fixed effects for country, study week as a categorical variable, baseline score, treatment, treatment by study week, and baseline by study week interactions, assuming an unstructured covariance matrix.
b: Treatment comparisons are based on an ANCOVA model including effects for treatment, country, and with the corresponding baseline as covariates.
: Source: Study 001/002 Clinical Study Report.²⁶

Table 23Summary of Absolute “On” “Off” Time (Full Analysis Set)

End Point	Study 001/002
End Point	LCIG + PBO IR OLC Capsules N = 36	PBO LCIG + IR OLC Capsules N = 33
Absolute “off” time, hours per day
Baseline, n (%)	35 (97)	31 (94)
Baseline, mean (SD)	6.63 (2.08)	7.51 (2.74)
Adjusted LS mean change from baseline at week 12 (SE)	−4.46 (0.74)	−2.18 (0.74)
Adjusted LS mean difference in change from baseline versus comparator (95% CI)	−2.28 (−3.58 to −0.98), P = 0.0009
Absolute “on” time without troublesome dyskinesia, hours per day
Baseline, n (%)	35 (97)	31 (94)
Baseline, mean (SD)	9.09 (2.26)	8.64 (2.29)
Adjusted LS mean change from baseline at week 12 (SE)	4.08 (0.78)	2.48 (0.79)
Adjusted LS mean difference in change from baseline versus comparator (95% CI)	1.60 (0.25, 2.95), P = 0.0207
Absolute “on” time without dyskinesia, hours per day
Baseline, n (%)	35 (97)	31 (94)
Baseline, mean (SD)	6.63 (2.77)	6.24 (3.32)
Adjusted LS mean change from baseline at week 12 (SE)	3.29 (1.11)	1.10 (1.11)
Adjusted LS mean difference in change from baseline versus comparator (95% CI)	2.19 (0.28 to 4.11), P = 0.0255
Absolute “on” time with non-troublesome dyskinesia, hours per day
Baseline, n (%)	35 (97)	31 (94)
Baseline, mean (SD)	2.46 (1.92)	2.41 (2.19)
Adjusted LS mean change from baseline at week 12 (SE)	1.01 (0.88)	1.77 (0.88)
Adjusted LS mean difference in change from baseline versus comparator (95% CI)	−0.77 (−2.29 to 0.76), P = 0.3183
Absolute “on” time with troublesome dyskinesia, hours per day
Baseline, n (%)	35 (97)	31 (94)
Baseline, mean (SD)	0.99 (1.63)	1.08 (1.55)
Adjusted LS mean change from baseline at week 12 (SE)	−0.07 (0.57)	0.04 (0.57)
Adjusted LS mean difference in change from baseline versus comparator (95% CI)	−0.11 (−1.09 to 0.87), P = 0.8274

: ANCOVA = analysis of covariance; CI = confidence interval; IR = immediate-release; LCIG = levodopa/carbidopa intestinal gel; LS = least squares; OLC = oral levodopa/carbidopa; PBO = placebo; SD = standard deviation; SE = standard error.
: Note: The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 0-hour to 16-hour scale (i.e., 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis.
: Treatment comparisons are based on an ANCOVA model including effects for treatment and country and using the corresponding baseline as covariates.
: Source: Study 001/002 Clinical Study Report.²⁶

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Clinical Review Report: Levodopa/Carbidopa (Duodopa): (Abbvie Corporation): Indication: For the treatment of patients with advanced levodopa-responsive Parkinson’s disease who do not have satisfactory control of severe, debilitating motor fluctuations and hyper-/dyskinesia despite optimized treatment with available combinations of Parkinson’s medicinal products, and, for whom the benefits of this treatment may outweigh the risks associated with the insertion and long-term use of the percutaneous endoscopic gastrostomy-jejunostomy (PEG-J) tube required for administration [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Sep. Appendix 4, Detailed Outcome Data.
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