Walking impairment in patients with multiple sclerosis – a new therapeutic approach and clinical potential of dalfampridine extended release tablets

Figures & data

Table 1 Mean (±standard deviation) single-dose pharmacokinetic parameters of immediate-release formulations of 4-aminopyridine (4-AP) and dalfampridine extended release 10 mg tablets

Pharmacokinetic parameter	Immediate- release 4-AP 10 mg (N = 6)^Citation41	Dalfampridine extended release 10 mg
		Healthy volunteers (N = 5)^Citation42	Patients with MS (N = 24)^Citation43
tmax, h	1.2 ± 0.4	3.2 ± 1.5	3.9 ± 1.2
Cmax, ng/mL	46.4 ± 9.7	21.6 ± 3.89	25.2 ± 6.8
t1/2, h	3.7 ± 0.7	6.4 ± 1.31	5.6 ± 2.2
AUC0-∞, ng ·h/mL	184.6 ± 24.0	284.8 ± 31.78	283.2 ± 88.2

Abbreviations: AUC, area under the curve; MS, multiple sclerosis.

Figure 1 Proportion of timed 25-foot walk (T25FW) responders in the pooled analysis and component studies (modified intent-to-treat population).⁶⁷

Note: Efficacy comparisons between placebo and dalfampridine-ER were performed using analysis of variance models with main effects for treatment group and center in the individual studies, main effects for treatment group, study, and center in the pooled analysis.
Abbreviation: MS, multiple sclerosis; ER, extended release.

Figure 2 Average percent change from baseline during the treatment period in walking speed among dalfampridine extended release (ER) responders relative to placebo group and dalfampridine-ER nonresponders in the pooled analysis and component studies (modified intent-to-treat population).⁶⁶

Abbreviation: MS, multiple sclerosis; ER, extended release.

Figure 3 Pooled analysis of timed-walk responder rate stratified by baseline demographic characteristics (modified intent-to-treat population).⁶⁷ (A) Gender. (B) Race. (C) Age. (D) Body mass index.

Abbreviation: ER, extended release.

Figure 4 Pooled analysis of timed-walk responder rate stratified by multiple sclerosis (MS) disease characteristics (modified intent-to-treat population).⁶⁷ (A) MS type. Relapsing remitting (RR), secondary progressive (SP), primary progressive (PP), progressive relapsing (PR). Because of the low number of patients with progressive-relapsing MS, the analysis of treatment by MS disease course type was computed post hoc, using only the RR, PP, and SP patients. (B) MS duration stratified by quartiles: Q1, ≥0.1 to <6.2 years; Q2, ≥6.2 to <10.8 years; Q3, ≥10.8 to <15.5 years; Q4, ≥15.5 years to 45.6 years (maximum).

Abbreviation: ER, extended release.

Figure 5 Percent change from baseline in walking speed in the parent studies and open-label long-term extensions by double-blind dalfampridine extended release (ER) responder status. (A) MS-F203. (B) MS-F204.

Abbreviations: DNR, dalfampridine-ER nonresponders; DR, dalfampridine-ER responders.

Figure 6 Percent change from baseline in walking speed by double-blind dalfampridine-ER responder status among those patients with continuous participation. (A) At week 104 in MS-F203. (B) At week 96 in MS-F204.

Abbreviations: ER, extended release; DNR, dalfampridine-ER nonresponders; DR, dalfampridine-ER responders.

Table 2 Treatment-emergent adverse events (TEAEs) that occurred in ≥5% of dalfampridine extended release (ER)-treated patients in the pooled MS-F202, MS-F203, and MS-F204 safety populationa

TEAEs	Incidence, n (%)
	Dalfampridine-ER 10 mg twice daily (n = 400)	Placebo (n = 238)
Any TEAE	339 (84.8)	175 (73.5)
Serious TEAE	22 (5.5)	5 (2.1)
Fall	64 (16.0)	39 (16.4)
Urinary tract infection	58 (14.5)	22 (9.2)
Insomnia	37 (9.3)	9 (3.8)
Asthenia	33 (8.3)	10 (4.2)
Dizziness	31 (7.8)	10 (4.2)
Headache	30 (7.5)	10 (4.2)
Nausea	28 (7.0)	6 (2.5)
Fatigue	26 (6.5)	11 (4.6)
Balance disorder	23 (5.8)	3 (1.3)
Upper respiratory tract infection	23 (5.8)	17 (7.1)
MS relapseb	21 (5.3)	9 (3.8)
Back pain	22 (5.5)	5 (2.1)

Notes:

a Includes off-drug, washout periods;

b similar incidences in drug and placebo groups during active treatment.

Abbreviation: MS, multiple sclerosis.

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