Evaluation of cardiovascular parameters in cynomolgus monkeys following IV administration of LBR-101, a monoclonal antibody against calcitonin gene-related peptide

Figures & data

Figure 1. Hemodynamic data from single dose telemetry study of LBR-101 in monkeys. Data are shown with 95% confidence intervals. (A) group mean systolic blood pressure; (B) change in SBP vs vehicle; (C) group mean diastolic blood pressure; (D) change in DBP vs vehicle.

Figure 2. Heart rate data from single dose telemetry study of LBR-101 in monkeys. Data are shown with 95% confidence intervals. (A) group mean heart rate; (B) change in heart rate vs vehicle.

Figure 3. Hemodynamic data from a 14-wk, repeat dose study of LBR-101 in monkeys. Data are shown with 95% confidence intervals. (A) systolic blood pressure; (B) diastolic blood pressure; (C) heart rate; (D) time-concentration profile at Weeks 1 and 13.

Table 1. Group mean ECG parameters in single-dose cardiovascular safety study in monkeys

Time Interval	Treatment Day	RR (msec)	PR (msec)	QRS (msec)	QT (msec)	QTc (msec)
Hours 1 – 4	Vehicle	481.37	111.63	38.00	243.13	177.13
	Day 1	513.25*	116.25*	38.38	254.88*	180.25
	Day 3	553.00*	118.38*	38.13	264.75*	171.63
	Day 7	561.00*	119.38*	39.00*	269.00*	172.39
	Day 10	538.00*	116.88*	38.88*	261.25*	174.63
	Day 14	550.50*	118.00*	39.00*	264.87*	171.75
Hours 5 – 7	Vehicle	502.38	119.62	39.50	249.38	174.38
	Day 1	511.25	121.12	38.88	251.63	177.25
	Day 3	514.25	118.62	38.75	254.13	174.13
	Day 7	513.25	117.87	39.50	253.75	174.36
	Day 10	498.38	117.25	39.00	251.38	180.38
	Day 14	513.25	119.75	39.13	253.88	175.12
Hours 7 – 18	Vehicle	602.25	120.00	39.63	299.38	185.25
	Day 1	624.38	122.50*	39.38	310.00	193.25
	Day 3	631.50*	119.88	39.25	306.38	180.13
	Day 7	663.75*	121.38	39.88	312.50*	177.07
	Day 10	602.38	120.38	39.63	299.88	190.00
	Day 14	659.38*	123.87*	39.75	314.00*	179.87
Hours 18 – 22	Vehicle	541.37	115.50	38.88	273.38	183.50
	Day 1	598.25*	119.25*	39.00	294.25*	188.13
	Day 3	604.62*	117.00	39.00	295.38*	178.75
	Day 7	646.25*	119.62*	39.13	305.88*	178.25
	Day 10	597.37*	119.50*	39.25	296.00*	188.25
	Day 14	644.25*	120.62*	39.25	307.88*	179.63

* P < 0.05 compared with vehicle treatment

Table 2. Group mean ECG parameters in a 14-wk, repeat-dose safety study in monkeys

Time	Treatment	RR (msec)	PR (msec)	QRS (msec)	QT (msec)	QTc (msec)
Pre-Study	Vehicle	334	81	38	197	341
	10 mg/kg	314	78	36	186	333
	100 mg/kg	335	88	37	197	341
	300 mg/kg	330	82	38	198	345
Pre-dose (Day 85)	Vehicle	344	83	40	204	348
	10 mg/kg	340	83	36	198	341
	100 mg/kg	337	91	38	199	343
	300 mg/kg	328	80	37	197	344
Post-dose (Day 85)	Vehicle	342	82	39	201	344
	10 mg/kg	327	82	37	196	343
	100 mg/kg	331	92	38	200	344
	300 mg/kg	349	86	37	204	345
Recovery Day 103	Vehicle	303	92	37	185	336
	10 mg/kg	318	83	33	188	334
	100 mg/kg	313	99	40	189	338
	300 mg/kg	299	90	34	183	335

Figure 4. Study schematics. (A) single-dose study; (B): repeat-dose study.