Phase 1
Completed N=20
A Drug Interaction Study to Assess the Effect of LY2603618 on the Metabolic Pathway of Desipramine
Source: ClinicalTrials.gov NCT01358968 ↗Enrolled (actual)
20
Serious AEs
12.1%
Results posted
Oct 2018
Primary outcomePrimary: Plasma Pharmacokinetics of LY2603618: the Maximum Concentration of LY2603618 in the Plasma (Cmax) — 5950 nanograms/milliliter (ng/mL)
Summary
The purpose of this study is to assess the effect LY2603618 on a protein [enzyme cytochrome P (CYP) 2D6] which is involved in the metabolic pathway of Desipramine in participants with cancer. This is a drug interaction study so the treatment of the disease will not be the main purpose of the study.
The study involves two single doses of 50 milligrams (mg), 1 tablet by mouth, on Day 1 of Period 1 and 2. In Period 1 Desipramine will be administered alone. In Period 2 Desipramine will be administered in combination with LY2603618. LY2603618 will be administered as a 275mg intravenous (IV) infusion over 1 hour (hr).
Desipramine will be administered at the end of the LY2603618 infusion. Information about any side effects that may occur will also be collected.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Plasma Pharmacokinetics of LY2603618: the Maximum Concentration of LY2603618 in the Plasma (Cmax) |
5950 | — |
| PRIMARY Plasma Pharmacokinetics of Desipramine: the Maximum Concentration of Desipramine in the Plasma (Cmax) |
21.2; 22.8 | — |
| PRIMARY Plasma Pharmacokinetics of LY2603618: the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] |
53700 | — |
| PRIMARY Plasma Pharmacokinetics of Desipramine: the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] |
655; 687 | — |
| PRIMARY Plasma Pharmacokinetics of LY2603618: the Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Observed Plasma Concentration of LY2603618 [AUC(0-tlast)] |
53000 | — |
| PRIMARY Plasma Pharmacokinetics of Desipramine: the Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Observed Plasma Concentration of Desipramine [AUC(0-tlast)] |
619; 653 | — |
| SECONDARY Number of Participants With a Tumor Response |
1; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Have a histological or cytological diagnosis of cancer (solid tumor), with clinical or radiologic evidence of locally advanced and/or metastatic disease, for which no life-prolonging therapy exists (that is, refractory to standard therapy and/or therapies known to provide clinical benefit, or for which no standard therapy exists). Note: Participants who have had progressive disease after receiving pemetrexed for metastatic disease are excluded from receiving the combination with pemetrexed during the safety extension study. Participants who have had progressive disease after receiving gemcitabine for metastatic disease are excluded from receiving the combination with gemcitabine during the safety extension study.
- Have a body surface area (BSA) greater than or equal to 1.37 square meters (m²)
- Have given written informed consent prior to any study-specific procedures
- Have adequate hematologic, hepatic and renal function
- Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
- Have discontinued all previous treatments for cancer, including chemotherapy, radiotherapy, anticancer hormone therapy or other investigational therapy for at least 30 days prior to study entry and recovered from the acute effects of therapy (at least 42 days for mitomycin-C or nitrosoureas, or 60 days for biologics)
- Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
- Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for at least 3 months following the last dose of study drug
- Females with childbearing potential: Have had a negative serum pregnancy test less than or equal to 7 days before the first dose of study drug and must also not be breastfeeding
- Have an estimated life expectancy, in the judgment of the investigator, that will permit the participant to complete 1 full cycle of treatment beyond the drug interaction portion of the study (approximately 8 weeks)
- Are able to swallow tablets
- Prior radiation therapy for treatment of cancer is allowed to 500 milliseconds (msec) on screening electrocardiogram (ECG)
- Have ECG abnormalities on the screening ECG such as significant conduction abnormalities, ischemic changes (such as prior Q-wave myocardial infarction and/or marked ischemic ST- and T-wave), arrhythmias (such as persistent or paroxysmal ventricular or supraventricular arrhythmias, including atrial fibrillation), or other ECG abnormalities that would put the participant at unnecessary risk in the opinion of the investigator
- Drugs with narrow therapeutic windows and that are also known substrates of CYP2D6 or drugs that are classified as sensitive substrates of CYP2D6 are excluded
- Drugs or herbal supplements that are known inhibitors of CYP2D6 are excluded during the study, and during the 30-day period (or a minimum of 5 half-lives, whichever is less) prior to study start
- Participants who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or participants unwilling to stop alcohol consumption for 24 hours before the study through the end of the study
Data sourced from ClinicalTrials.gov (NCT01358968). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.