Table 2.
Key parameter estimates (coefficient of variation (CV)%) of LY3045697 plasma concentration-response models for various basal and stimulated pharmacodynamic (PD) endpoints.
| Basal |
Stimulated |
|||||
|---|---|---|---|---|---|---|
| Single dose |
Multiple dose |
Post-ACTH |
Post-K+ challenge |
|||
| PAC | K+ | PAC | K+ | PAC | K+ | |
| Placebo response (pg/ml for PAC; mM for K+) |
52 (5.9%) | 4.5 (0.8%) | 98 (8.3%) | 4.3 (1.2%) | 73 (18%) | 4.4 (1.1%) |
| Maximum LY3045697 effecta
(fractional reduction for PAC; mM for K+) |
0.90 (0.8%) | 0.12 (47%) | 0.94 (1.4%) | 0.70 (14%) | 1.1 (4.1%) | 0.58 (12%) |
| LY3045697 C50b
(ng/ml) |
0.60 (18%) | 1.3 (180%)c | 28 (20%) | 4.3 (46%) | 0.38 (32%) | 10 (50%) |
| Spironolactone (50 mg) effect (pg/ml for PAC; mM for K+)a |
NA | NA | 49 (19%) | 0.02 (232%) | 18 (89%) | 0.09 (68%) |
ACTH: adrenocorticotropic hormone; K+: potassium ion; PAC: plasma concentration of aldosterone.
a
Maximum drug effect for PAC (Imax) was modeled as a fractional reduction (e.g. 0.9 means 90% reduction) relative to placebo response, while for K+ (Emax) as an additive effect above placebo response (e.g. 0.12 mM means 0.12 mM above that observed for placebo).
b
The plasma concentration at 50% of the effect (i.e. IC50 for inhibitory effect on PAC or EC50 for stimulatory effect on K+).
c
Poorly estimated due to low maximum response.