Background
Methods
Participants and study design
Measures and statistical analyses
Results
Study population
MS-LAQ-101 | Pooled placebo (n = 28) | Laquinimod 0.9 mg (n = 12) | Laquinimod 1.2 mg (n = 12) | Laquinimod 1.5 mg (n = 12) | Laquinimod 1.8 mg (n = 11) | Laquinimod 2.1 mg (n = 13) | Laquinimod 2.4 mg (n = 12) | Laquinimod 2.7 mg (n = 12) | All (N = 112) |
---|---|---|---|---|---|---|---|---|---|
Age, years | |||||||||
Mean ± SD | 37.3 ± 8.5 | 38.6 ± 10.3 | 35.8 ± 9.4 | 35.2 ± 5.3 | 35.5 ± 8.4 | 41.5 ± 9.8 | 38.3 ± 10.5 | 44.8 ± 7.5 | 38.3 ± 9.0 |
Range | 20.9–53.9 | 21.4–55.9 | 18.6–48.4 | 28.8–44.8 | 23.2–47.2 | 23.4–56.0 | 23.6–54.5 | 31.3–55.5 | 18.6–56.0 |
Gender N (%) | |||||||||
Female | 23 (82.1) | 10 (83.3) | 6 (50.0) | 10 (83.3) | 5 (45.5) | 7 (53.8) | 9 (75.0) | 9 (75.0) | 79 (70.5) |
Male | 5 (17.9) | 2 (16.7) | 6 (50.0) | 2 (16.7) | 6 (54.5) | 6 (46.2) | 3 (25.0) | 3 (25.0) | 33 (29.5) |
Height (cm) | |||||||||
Mean ± SD | 170.3 ± 9.5 | 174.2 ± 9.8 | 175.8 ± 8.5 | 169.6 ± 8.1 | 177.7 ± 10.5 | 171.9 ± 7.9 | 171.4 ± 7.7 | 173.1 ± 6.8 | 172.6 ± 8.9 |
Range | 157.0–196.0 | 158.0–198.0 | 164.0–196.0 | 158.0–180.0 | 158.0–193.0 | 158.0–186.5 | 161.0–186.0 | 164.0–187.0 | 157.0–198.0 |
Weight (kg) | |||||||||
Mean ± SD | 72.9 ± 15.3 | 74.8 ± 14.5 | 75.9 ± 17.4 | 77.7 ± 19.1 | 81.1 ± 18.6 | 81.0 ± 13.9 | 79.9 ± 9.9 | 77.4 ± 12 | 76.9 ± 15.2 |
Range | 53.0–110.0 | 57.0–99.5 | 58.0–124.0 | 52.0–113.0 | 63.0–123.2 | 62.0–109.5 | 62.0–98.0 | 62.0–97.0 | 52.0–124.0 |
BMI (kg/m2) | |||||||||
Mean ± SD | 24.9 ± 3.7 | 24.8 ± 5.5 | 24.4 ± 4.3 | 27.0 ± 6.4 | 25.7 ± 5.0 | 27.4 ± 4.2 | 27.3 ± 3.9 | 25.8 ± 3.6 | 25.8 ± 4.5 |
Range | 20.2–36.6 | 19.8–39.9 | 18.9–32.3 | 18.6–36.5 | 19.1–35.8 | 21.1–33.0 | 22.0–33.9 | 21.5–33.6 | 18.6–39.9 |
EDSS score at screening | |||||||||
Mean ± SD | 2.1 ± 1.1 | 2.0 ± 1.4 | 1.6 ± 1.2 | 2.1 ± 1.3 | 2.4 ± 1.8 | 2.5 ± 1.2 | 2.7 ± 1.0 | 2.6 ± 1.5 | – |
Range | 0.0–5.5 | 0.5–5.5 | 0.0–4.0 | 0.0–5.5 | 0.0–5.5 | 1.0–5.0 | 1.0–4.0 | 1.0–5.5 | – |
Total number of exacerbations in the year prior to screening | |||||||||
Mean ± SD | 0.7 ± 0.6 | 1.2 ± 0.8 | 1.1 ± 0.8 | 0.8 ± 0.7 | 1.2 ± 1.2 | 1.0 ± 0.9 | 1.0 ± 0.6 | 1.0 ± 0.6 | 0.9 ± 0.8 |
Range | 0.0–2.0 | 0.0–3.0 | 0.0–3.0 | 0.0–2.0 | 0.0–4.0 | 0.0–3.0 | 0.0–2.0 | 0.0–2.0 | 0.0–4.0 |
Safety and tolerability
MS-LAQ-101 % of patients Preferred term | Pooled placebo (n = 28) | Laquinimod 0.9 mg (n = 12) | Laquinimod 1.2 mg (n = 12) | Laquinimod 1.5 mg (n = 12) | Laquinimod 1.8 mg (n = 11) | Laquinimod 2.1 mg (n = 13) | Laquinimod 2.4 mg (n = 12) | Laquinimod 2.7 mg (n = 12) |
---|---|---|---|---|---|---|---|---|
All | 96.4 | 75 | 100 | 83.3 | 90.9 | 92.3 | 100 | 100 |
Headache | 32.1 | 50 | 66.7 | 41.7 | 18.2 | 38.5 | 91.7 | 41.7 |
C-reactive protein increased | 7.1 | 16.7 | 16.7 | 8.3 | 0 | 7.7 | 8.3 | 33.3 |
Vomiting | 0 | 0 | 0 | 8.3 | 0 | 7.7 | 0 | 33.3 |
Abdominal pain upper | 10.7 | 0 | 16.7 | 8.3 | 9.1 | 7.7 | 33.3 | 25 |
Back pain | 0 | 16.7 | 0 | 16.7 | 0 | 7.7 | 25 | 25 |
Blood fibrinogen increased | 0 | 0 | 16.7 | 0 | 0 | 7.7 | 0 | 25 |
Myalgia | 0 | 0 | 0 | 0 | 9.1 | 0 | 8.3 | 25 |
Nausea | 7.1 | 8.3 | 0 | 8.3 | 0 | 7.7 | 25 | 25 |
Tension headache | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 25 |
Diarrhea | 7.1 | 8.3 | 8.3 | 8.3 | 9.1 | 15.4 | 8.3 | 16.7 |
Insomnia | 0 | 0 | 0 | 0 | 0 | 0 | 8.3 | 16.7 |
Blood creatine Phosphokinase increased | 14.3 | 0 | 8.3 | 8.3 | 18.2 | 0 | 0 | 8.3 |
Nasopharyngitis | 10.7 | 16.7 | 33.3 | 8.3 | 0 | 38.5 | 8.3 | 8.3 |
Oropharyngeal pain | 0 | 0 | 0 | 0 | 18.2 | 0 | 0 | 8.3 |
Pain in extremity | 0 | 8.3 | 8.3 | 0 | 18.2 | 0 | 0 | 8.3 |
Dizziness | 10.7 | 0 | 8.3 | 0 | 9.1 | 0 | 25 | 0 |
Contusion | 0 | 0 | 0 | 0 | 0 | 7.7 | 16.7 | 0 |
Pharmacokinetics
Dose (mg) |
n
|
t
max
a (h) |
C
max (ng/mL) |
C
min (ng/mL) | AUC0–24 (ng h/mL) | Dose -normalized | |
---|---|---|---|---|---|---|---|
C
max
| AUC0–24h
| ||||||
0.9 | 10 | 0.99 (0.25–2.00) | 639.6 ± 114.9 | 469.5 ± 103.4 | 12,245.8 ± 2075.4 | 710.6 ± 127.6 | 13,606.5 ± 2306.0 |
1.2 | 12 | 0.75 (0.25–4.00) | 779.2 ± 115.7 | 565.7 ± 121.0 | 15,075.2 ± 2757.6 | 649.4 ± 96.4 | 12,562.7 ± 2298.0 |
1.5 | 12 | 1.00 (0.50–24.00) | 1207.8 ± 210.8 | 904.0 ± 189.5 | 22,974.0 ± 3756.6 | 805.2 ± 140.6 | 15,316.0 ± 2504.4 |
1.8 | 11 | 0.50 (0.25–3.00) | 1449.4 ± 325.4 | 1076.7 ± 274.3 | 28,042.7 ± 6495.5 | 805.2 ± 180.8 | 15,579.3 ± 3608.6 |
2.1 | 11 | 2.00 (0.50–6.00) | 1712.1 ± 385.8 | 1310.5 ± 356.0 | 33,741.2 ± 8133.4 | 815.3 ± 183.7 | 16,067.2 ± 3873.1 |
2.4 | 10 | 0.50 (0.50–2.00) | 1892.3 ± 526.3 | 1389.3 ± 512.9 | 35,470.0 ± 11,100.2 | 788.5 ± 219.3 | 14,779.2 ± 4625.1 |
2.7 | 10 | 1.00 (0.5–2.00) | 1826.2 ± 313.4 | 1364.5 ± 186.7 | 35,274.5 ± 5973.0 | 676.4 ± 116.1 | 13,064.6 ± 2212.2 |
Immunological substudy
Placebo | Laquinimod | |||||
---|---|---|---|---|---|---|
Parameter |
n
| Mean | Std Err |
n
| Mean | Std Err |
SlanDC CD83-culture LPS (%) difference from baseline | 13 | −2.3 | 5.6 | 31 | −18.8 | 4.2 |
SlanDC CD83-culture R848 (%) difference from baseline | 13 | −5.5 | 6.4 | 31 | −16.5 | 3.2 |
SlanDC TNF-culture LPS (%) difference from baseline | 15 | −3.0 | 3.2 | 37 | −9.4 | 2.5 |
SlanDC TNF-culture R848 (%) difference from baseline | 15 | −2.3 | 3.1 | 37 | −8.9 | 2.3 |