Effect of a change in lasmiditan dose on efficacy and safety in patients with migraine

Figures & data

Figure 1. Study designs of SAMURAI, SPARTAN, and GLADIATOR

^aLTN 50-mg dose included in SPARTAN only. Abbreviation: LTN = lasmiditan.

Table 1. Baseline patient characteristics and demographics

Group	Treatment Groups (SPARTAN or SAMURAI to GLADIATOR)
	PBO to LTN 100 mg	PBO to LTN 200 mg	LTN 50 mg to LTN 100 mg	LTN 50 mg to LTN 200 mg	LTN 100 mg to LTN 100 mg	LTN 100 mg to LTN 200 mg	LTN 200 mg to LTN 100 mg	LTN 200 mg to LTN 200 mg
N	272	304	159	161	260	262	239	235
Age, years, mean (SD)	42.1 (12.4)	43.2 (12.2)	41.7 (12.5)	45.1 (13.5)	42.9 (12.3)	42.5 (11.8)	41.4 (11.8)	42.4 (12.5)
Female, n (%)	233 (85.7)	262 (86.2)	141 (88.7)	138 (85.7)	222 (85.4)	223 (85.1)	199 (83.3)	200 (85.1)
Non-Caucasian, n (%)	46 (16.9)	66 (21.7)	34 (21.4)	24 (14.9)	70 (26.9)	46 (17.6)	57 (23.8)	53 (22.6)
Baseline Pain, n (%)	-	-	-	-	-	-	-	-
Severe	71 (26.1)	88 (28.9)	33 (20.8)	45 (28.0)	65 (25.0)	69 (26.3)	66 (27.6)	78 (33.2)
Moderate	194 (71.3)	211 (69.4)	121 (76.1)	112 (69.6)	187 (71.9)	190 (72.5)	171 (71.5)	156 (66.4)
Mild	7 (2.6)	5 (1.6)	5 (3.1)	4 (2.5)	8 (3.1)	3 (1.1)	2 (0.8)	1 (0.4)
Duration of migraine history, years, mean (SD)	18.2 (12.2)	19.4 (13.2)	19.3 (11.8)	19.3 (13.1)	19.3 (13.8)	18.0 (13.0)	18.7 (12.7)	17.9 (12.8)
Average migraines/month in past 3 months, mean (SD)	5.3 (1.9)	5.2 (1.7)	5.1 (1.7)	5.2 (2.1)	5.2 (1.8)	5.1 (1.8)	5.3 (1.7)	5.2 (1.7)

Data from the safety population is presented.

Abbreviations: PBO = placebo, LTN = lasmiditan; N = number of patients with non-missing assessments; n = number of patients within each specific category; SD = standard deviation.

Figure 2. Efficacy outcomes for the first dose and subsequent dose

*p-Value <0.05.The first dose is the dose that was received for treating the attack in SAMURAI or SPARTAN and the subsequent dose was the dose received for treating the first attack in GLADIATOR. Difference is the percentage in GLADIATOR minus the percentage in pooled SAMURAI or SPARTAN studies. Efficacy outcomes reported at 2 h after dosing. Abbreviations: MBS = most bothersome symptom; PBO = placebo.

Figure 3. Incidence of patients who experienced at least one MC- TEAE with the first dose and subsequent dose

*p-Value <0.05. First dose is the dose that was received for treating the attack in SAMURAI or SPARTAN and the subsequent dose was the dose received for treating the first attack in GLADIATOR. Difference is the percentage in GLADIATOR minus the percentage in pooled SAMURAI or SPARTAN studies. MC-TEAEs reported within 48 hours after first dose for the first treated migraine attack of each study were counted. Abbreviations: MC-TEAE = most common treatment-emergent adverse event; PBO = placebo.

Table 2. Efficacy-TEAE balance change from first dose to subsequent dose

SPARTAN/SAMURAI to GLADIATOR	Percent Change from 1st Dose to 2nd Dose
Treatment Groups	Efficacy				Safety
	Pain Free	Disability Free	MBS Free	Pain Relief	≥1 MC-TEAE
PBO to LTN 100 mg	+14.3	+13.4	+16.9	+17.6	+11.8
PBO to LTN 200 mg	+6.3	+6.0	+8.3	+19.8	+15.8
LTN 50 mg to LTN 100 mg	+1.9	+3.0	+0.8	+9.6	+6.3
LTN 50 mg to LTN 200 mg	+5	+4.2	+10.9	+11.5	+4.4
LTN 100 mg to LTN 100 mg	-2.7	-3.5	-0.5	+3.0	-9.6
LTN 100 mg to LTN 200 mg	+5.9	+5.7	+5.4	+5.1	-0.4
LTN 200 mg to LTN 100 mg	-7.7	-0.5	-2.4	+7.7	-9.6
LTN 200 mg to LTN 200 mg	-6.1	-5.6	+0.6	+1.0	-5.5

Color code: green = increased percentage in difference from first dose to subsequent dose in incidence of efficacy assessment (pain freedom, disability freedom, MBS freedom, pain relief) or decreased percentage in incidence of ≥1 MC-TEAE (not MC-TEAE free); red = decreased percentage in difference from first dose to subsequent dose in incidence of efficacy assessment or increased percentage in incidence of ≥1 MC-TEAE (not MC-TEAE free)

Abbreviations: LTN = lasmiditan; MBS = most bothersome symptom; MC-TEAE = most common treatment-emergent adverse event; PBO = placebo.

Table 3. Pain freedom (a), Disability freedom (b), Most bothersome symptom freedom (c), Pain relief (d), and Most common treatment-emergent adverse event MC-TEAE freedom (e) – Distribution of patients in each of four outcome shift categories by dose scheme

(a) SAMURAI/SPARTAN to GLADIATOR		Pain Freedom Shift Category
Treatment Group	N ^a	Pain Free to Pain Free	Pain Free to Not Pain Free	Not Pain Free to Not Pain Free	Not Pain Free to Pain Free
PBO to LTN 100 mg	266	36 (13.5%)	18 (6.8%)	156 (58.6%)	56 (21.1%)
PBO to LTN 200 mg	302	42 (13.9%)	34 (11.3%)	173 (57.3%)	53 (17.5%)
LTN 50 mg to LTN 100 mg	156	24 (15.4%)	22 (14.1%)	85 (54.5%)	25 (16.0%)
LTN 50 mg to LTN 200 mg	160	27 (16.9%)	26 (16.3%)	73 (45.6%)	34 (21.3%)
LTN 100 mg to LTN 100 mg	255	39 (15.3%)	42 (16.5%)	139 (54.5%)	35 (13.7%)
LTN 100 mg to LTN 200 mg	256	36 (14.1%)	40 (15.6%)	125 (48.8%)	55 (21.5%)
LTN 200 mg to LTN 100 mg	234	48 (20.5%)	46 (19.7%)	112 (47.9%)	28 (12.0%)
LTN 200 mg to LTN 200 mg	229	50 (21.8%)	47 (20.5%)	99 (43.2%)	33 (14.4%)
(b) SAMURAI/SPARTAN to GLADIATOR		Disability Freedom Shift Category
Treatment Group	N ^a	Disability Free to Disability Free	Disability Free to Not Disability Free	Not Disability Free to Not Disability Free	Not Disability Free to Disability Free
PBO to LTN 100 mg	239	39 (16.3%)	20 (8.4%)	128 (53.6%)	52 (21.8%)
PBO to LTN 200 mg	250	43 (17.2%)	34 (13.6%)	124 (49.6%)	49 (19.6%)
LTN 50 mg to LTN 100 mg	132	28 (21.2%)	16 (12.1%)	68 (51.5%)	20 (15.2%)
LTN 50 mg to LTN 200 mg	142	32 (22.5%)	20 (14.1%)	64 (45.1%)	26 (18.3%)
LTN 100 mg to LTN 100 mg	227	41 (18.1%)	42 (18.5%)	110 (48.5%)	34 (15.0%)
LTN 100 mg to LTN 200 mg	209	43 (20.6%)	30 (14.4%)	94 (45.0%)	42 (20.1%)
LTN 200 mg to LTN 100 mg	190	47 (24.7%)	31 (16.3%)	82 (43.2%)	30 (15.8%)
LTN 200 mg to LTN 200 mg	196	48 (24.5%)	38 (19.4%)	83 (42.3%)	27 (13.8%)
(c) SAMURAI/SPARTAN to GLADIATOR		MBS Freedom Shift Category
Treatment Group	N ^a	MBS Free to MBS Free	MBS Free to Not MBS Free	Not MBS Free to Not MBS Free	Not MBS Free to MBS Free
PBO to LTN 100 mg	219	54 (24.7%)	19 (8.7%)	90 (41.1%)	56 (25.6%)
PBO to LTN 200 mg	229	59 (25.8%)	27 (11.8%)	97 (42.4%)	46 (20.1%)
LTN 50 mg to LTN 100 mg	124	40 (32.3%)	18 (14.5%)	47 (37.9%)	19 (15.3%)
LTN 50 mg to LTN 200 mg	128	45 (35.2%)	17 (13.3%)	35 (27.3%)	31 (24.2%)
LTN 100 mg to LTN 100 mg	203	47 (23.2%)	42 (20.7%)	73 (36.0%)	41 (20.2%)
LTN 100 mg to LTN 200 mg	184	51 (27.7%)	29 (15.8%)	65 (35.3%)	39 (21.2%)
LTN 200 mg to LTN 100 mg	168	52 (31.0%)	34 (20.2%)	52 (31.0%)	30 (17.9%)
LTN 200 mg to LTN 200 mg	180	57 (31.7%)	32 (17.8%)	58 (32.2%)	33 (18.3%)
(d) SAMURAI/SPARTAN to GLADIATOR		Pain Relief Shift Category
Treatment Group	N ^a	Pain Relief to Pain Relief	Pain Relief to No Pain Relief	No Pain Relief to No Pain Relief	No Pain Relief to Pain Relief
PBO to LTN 100 mg	244	84 (34.4%)	31 (12.7%)	55 (22.5%)	74 (30.3%)
PBO to LTN 200 mg	258	105 (40.7%)	27 (10.5%)	48 (18.6%)	78 (30.2%)
LTN 50 mg to LTN 100 mg	136	73 (53.7%)	13 (9.6%)	24 (17.6%)	26 (19.1%)
LTN 50 mg to LTN 200 mg	148	75 (50.7%)	16 (10.8%)	24 (16.2%)	33 (22.3%)
LTN 100 mg to LTN 100 mg	231	107 (46.3%)	40 (17.3%)	37 (16.0%)	47 (20.3%)
LTN 100 mg to LTN 200 mg	214	109 (50.9%)	30 (14.0%)	34 (15.9%)	41 (19.2%)
LTN 200 mg to LTN 100 mg	195	102 (52.3%)	23 (11.8%)	32 (16.4%)	38 (19.5%)
LTN 200 mg to LTN 200 mg	203	107 (52.7%)	33 (16.3%)	28 (13.8%)	35 (17.2%)
(e) SAMURAI/SPARTAN to GLADIATOR		MC-TEAE Freedom Shift Category
Treatment Group	N^a	MC-TEAE Free to MC-TEAE Free	MC-TEAE Free to Not MC-TEAE Free	Not MC-TEAE Free to Not MC-TEAE Free	Not MC-TEAE Free to MC-TEAE Free
PBO to LTN 100 mg	272	216 (79.4)	42 (15.4)	4 (1.5)	10 (3.7)
PBO to LTN 200 mg	304	229 (75.3)	58 (19.1)	7 (2.3)	10 (3.3)
LTN 50 mg to LTN 100 mg	159	119 (74.8)	23 (14.5)	4 (2.5)	13 (8.2)
LTN 50 mg to LTN 200 mg	161	122 (75.8)	19 (11.8)	8 (5.0)	12 (7.5)
LTN 100 mg to LTN 100 mg	260	193 (74.2)	16 (6.2)	10 (3.8)	41 (15.8)
LTN 100 mg to LTN 200 mg	262	175 (66.8)	27 (10.3)	32 (12.2)	28 (10.7)
LTN 200 mg to LTN 100 mg	239	166 (69.5)	18 (7.5)	14 (5.9)	41 (17.2)
LTN 200 mg to LTN 200 mg	235	163 (69.4)	21 (8.9)	17 (7.2)	34 (14.5)

^aTotal number of patients for each dose change group and the denominator for all percentages shown.

The number of patients who shifted their response status from the first dose to the subsequent dose was summarized in each dose change group.

Abbreviations: LTN = lasmiditan; MBS = most bothersome symptom; MC-TEAE = most common treatment-emergent adverse event; PBO = placebo.

Figure 4. Incidence of pain-free patients after the subsequent dose among patients who were not pain-free after the initial dose (a); incidence of patients not MC-TEAE free after the subsequent dose among patients who were MC-TEAE free after the initial dose (b)

Other shift outcome combinations are not shown here, but data is available via Table 3(a–e) showing shifts such as pain-free to pain-free or not MC-TEAE free to not MC-TEAE free. The absolute difference between the percentages in the GLADIATOR study (from the subsequent dose) and the SAMURAI or SPARTAN studies (from the first dose) are shown. The denominator for the percentages shown is for all patients who were either not pain-free (a) or MC-TEAE free (b) after the first dose. Pain status was recorded at 2 hours post-dose. MC-TEAEs occurring within 48 hours after first dose for the first migraine attack of each study were counted. Abbreviations: LTN = lasmiditan; MC-TEAE = most common treatment-emergent adverse event.

Figure 5. Effect of changing lasmiditan dose on pain response based on pain outcome after the first treated attack

This Sankey shift figure shows patient pain freedom outcomes for patients treated with lasmiditan for a first (LTN 50, LTN 100, LTN 200) and subsequent dose [increased dose (50–100, 50–200, 100–200), same dose (100–100, 200–200), or decreased dose (200–100)]. The number of patients in the first and subsequent dose populations are shown. Additionally, the percentage of patients who are pain-free after their first and subsequent dose are shown. The ribbon height represents proportion of patients. Color code: black = LTN 50, dark gray = LTN 100, red = LTN 200; purple = increased dose, light gray = same dose, brown = decreased dose; green = pain free, yellow = not pain free. Abbreviation: LTN = lasmiditan.

Figure 6. Effect of changing lasmiditan dose on the percentage of patients experiencing a MC-TEAE based on whether a MC-TEAE was experienced with treatment of the first attack

This Sankey shift figure shows patient MC-TEAE freedom outcomes for patients treated with lasmiditan for a first (LTN 50, LTN 100, LTN 200) and subsequent dose [increased dose (50–100, 50–200, 100–200), same dose (100–100, 200–200), or decreased dose (200–100)]. The number of patients in the first and subsequent dose populations are shown. Additionally, the percentage of patients who are pain-free after their first and subsequent dose are shown. The ribbon height represents proportion of patients. Color code: black = LTN 50, dark gray = LTN 100, red = LTN 200; purple = increased dose, light gray = same dose, brown = decreased dose; green = pain free, blue = not pain free. Abbreviation: LTN = lasmiditan; MC-TEAE = most common treatment-emergent adverse event.

Data availability

Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the US and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.