Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01155661 | A Safety Study in Participants With Major Depressive Disorder | PHASE3 | COMPLETED | 608 | — | — | Oct 1, 2010 | Dec 1, 2012 | Apr 17, 2018 | 48 | United States, Brazil +5 |
| NCT00840034 | A Study of Adjunctive Treatment to Antidepressant Therapy for Adults With Major Depressive Disorder | PHASE2 | COMPLETED | 227 | — | — | Feb 1, 2009 | Jan 1, 2010 | Apr 24, 2018 | 24 | United States |
| NCT00795821 | A Study in Adult Patients With Major Depressive Disorder | PHASE2 | COMPLETED | 495 | — | — | Dec 1, 2008 | Mar 1, 2011 | Mar 20, 2018 | 37 | United States, Argentina +3 |
| NCT01460381 | A Study to Evaluate the Effect of Genotype on LY2216684 | PHASE1 | COMPLETED | 18 | — | — | Oct 1, 2011 | Aug 1, 2012 | Oct 26, 2018 | 1 | United States |
| NCT01460407 | A Study to Evaluate the Effect of Clarithromycin on LY2216684 | PHASE1 | COMPLETED | 14 | — | — | Oct 1, 2011 | Dec 1, 2011 | Oct 19, 2018 | 1 | United States |
| NCT01389752 | A Study to Evaluate the Effect of Activated Charcoal on the Absorption of LY2216684 in Healthy Subjects | PHASE1 | COMPLETED | 22 | — | — | Jul 1, 2011 | Sep 1, 2011 | Jan 4, 2019 | 1 | United States |
| NCT01389765 | A Study to Evaluate the Effect of Food on LY2216684 | PHASE1 | COMPLETED | 24 | — | — | Jul 1, 2011 | Aug 1, 2011 | Nov 13, 2018 | 1 | United States |
| NCT01373931 | A Study of LY2216684 in Healthy Females | PHASE1 | COMPLETED | 20 | — | — | Jun 1, 2011 | Dec 1, 2011 | Oct 23, 2018 | 1 | United States |
| NCT01241435 | A Study of LY2216684 in Participants With Impaired Hepatic Function | PHASE1 | COMPLETED | 36 | — | — | Oct 1, 2010 | Apr 1, 2011 | Oct 22, 2018 | 3 | United States |
A clinically significant effect was defined as a serious adverse event, regardless of causality. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS is a 10-item checklist with items rated on a scale of 0-6, for a total scores range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means are calculated using mixed model repeating measures (MMRM) and adjusted for investigator, treatment-by-visit, baseline score, and baseline-by-visit.
The MADRS measured severity of depressive mood symptoms. The 10-item checklist rating scale was 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.
Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.
Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.
AUC0-∞ of LY2216684 was calculated during Period 1, when 18-mg LY2216684 was administered alone and Period 2, when Clarithromycin was coadministered with LY2216684. The outcome was presented as geometric Least Squares (LS) mean and the 90% Confidence Interval (CI). Geometric LS mean was controlled by participant and treatment.
Cmax of LY2216684 was calculated during Period 1, when 18-mg LY2216684 was administered alone, and Period 2, when Clarithromycin was coadministered with LY2216684. The outcome was presented as geometric LS mean and the 90% CI. Geometric LS mean was controlled by participant and treatment.
Tmax of LY2216684 was calculated during Period 1, when 18-mg LY2216684 was administered alone, and Period 2, when Clarithromycin was coadministered with LY2216684. The outcome was presented as geometric LS mean and the 90% CI. Geometric LS mean was controlled by participant and treatment.
The Cmax of LY2216684 was assessed. The Cmax was calculated for LY2216684 administered alone (reference) and LY2216684 co-administered with charcoal (test). Geometric LSMeans were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for Cmax.
The results presented are Geometric Least Squares (LS) mean. LS mean values were adjusted for treatment, sequence, period and participant.
The results presented are Geometric Least Squares (LS) mean. LS mean values were adjusted for treatment, sequence, period and participant.
The area under the plasma concentration versus time curve from 0 hours to infinity (AUC \[0-∞\]) for LY2216684 is presented.
| Arm | Type | Description |
|---|---|---|
| LY2216684 (edivoxetine) + SSRI | EXPERIMENTAL | - |
| LY2216684 | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| LY2216684 + Quinidine (CYP2C19 poor metabolizers) | EXPERIMENTAL | Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 was administered on Day 1. Period 2 (Days 8-15): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11. |
| LY2216684 (CYP2C19 extensive metabolizers) | EXPERIMENTAL | Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 administered on Day 1. Period 2 (Days 8-15): EM participants did not participate in this period. |
| LY2216684 + Clarithromycin | EXPERIMENTAL | Participants will receive a single 18-mg oral dose of LY2216684 on Days 1 and 10. Clarithromycin (500 mg) will be administered twice a day (BID) on Days 6 through 13. |
| LY2216684 without Charcoal, then with Charcoal | EXPERIMENTAL | Period 1: Single 18-mg (milligram) (two 9-mg tablets) oral dose of LY2216684 administered without Activated Charcoal. Period 2: Single 18-mg (two 9-mg tablets) oral dose of LY2216684 administered with single oral dose of 1 g/kg (gram/kilogram) of Activated Charcoal. Periods will be separated by a minimum of 7 days. |
| LY2216684 with Charcoal, then without Charcoal | EXPERIMENTAL | Period 1: Single 18-mg (two 9-mg tablets) oral dose of LY2216684 administered with single oral dose of 1 g/kg of Activated Charcoal. Period 2: Single 18-mg (two 9-mg tablets) oral dose of LY2216684 administered without Activated Charcoal. Periods will be separated by a minimum of 7 days. |
| LY2216684 administered in fasted then fed state | EXPERIMENTAL | Period 1: Single 18-mg (milligram) oral dose of LY2216684 administered in fasted state. Period 2: Single 18-mg oral dose of LY2216684 administered in fed state. Periods will be separated by a minimum of 7 days. |
| LY2216684 administered in fed then fasted state | EXPERIMENTAL | Period 1: Single 18-mg oral dose of LY2216684 administered in fed state. Period 2: Single 18-mg oral dose of LY2216684 administered in fasted state. Periods will be separated by a minimum of 7 days. |
| OC + LY2216684 First, Then OC + Placebo | EXPERIMENTAL | 28-day lead-in period of Ortho Cyclen (OC; 28-day packet), followed by randomization to OC administered orally once daily for 28 days + 18 milligrams (mg) of LY2216684 administered concomitantly orally once daily for 21 days, followed by OC administered orally once daily for 28 days + placebo administered concomitantly orally once daily for 21 days. |
| OC + Placebo First, Then OC + LY2216684 | EXPERIMENTAL | 28-day lead-in period of OC (28-day packet), followed by randomization to OC administered orally once daily for 28 days + placebo administered concomitantly orally once daily for 21 days, followed by OC administered orally once daily for 28 days + 18 mg of LY2216684 administered concomitantly orally once daily for 21 days. |
| Name | Type | Description |
|---|---|---|
| LY2216684 (edivoxetine) | DRUG | 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) |
| SSRI | DRUG | Participants should have been on their SSRI for at least 6 weeks prior and were to continue on their stable dose throughout the study. |
| LY2216684 | DRUG | Starting dose is 6 milligrams (mg), then titrate up to 9 mg, 12 mg, or 18 mg (3 tablets) administered orally (PO), once daily (QD) for up to 10 weeks followed by a 2 week taper. |
| Placebo | DRUG | 3 tablets PO QD for up to 12 weeks |
| Quinidine | DRUG | - |
| Clarithromycin | DRUG | Administered orally |
| Activated Charcoal | DRUG | Administered orally |
| Ortho Cyclen | DRUG | 35 micrograms (mcg) ethinyl estradiol and 250 mcg norgestimate administered orally |
Inclusion Criteria: * Adults competent and able to give informed consent * Women of child-bearing potential may participate but must test negative for pregnancy at the time of study entry; both women/men agree to use a reliable method of birth control * Participants who are being treated with one o...