A Drug Interaction Study to Assess the Effect of LY2603618 on the Metabolic Pathway of Desipramine

• Register: ClinicalTrials.gov
• Last refreshed on: 21 January 2013
• Main ID: NCT01358968
• Date of registration: 20/05/2011
• Primary sponsor: Eli Lilly and Company
• Public title: A Drug Interaction Study to Assess the Effect of LY2603618 on the Metabolic Pathway of Desipramine
• Scientific title: A Study in Cancer Patients to Evaluate the Ability of LY2603618 to Act as an Inhibitor of CYP2D6 Using Desipramine as a Probe Substrate
• Date of first enrolment: June 2011
• Target sample size: 60
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01358968
• Study type: Interventional
• Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Call 1-877-CTLILLY (1-877-285-4559) or 1-371-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion 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: Patients who have had progressive disease after receiving pemetrexed
for metastatic disease are excluded from receiving the combination with pemetrexed
during the safety extension study. Patients 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 m^2

- 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 patient 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 <25% of the bone marrow
and patients must have recovered from the acute toxic effects of their treatment
prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior
radiotherapy must be completed at least 4 weeks before study entry.

Exclusion Criteria:

- Have received treatment within 28 days of the initial dose of study drug with an
experimental agent for noncancer indications that has not received regulatory
approval for any indication

- Poor metabolizer (PM) status for CYP2D6 (genotyped)

- Have previously completed or withdrawn from this study or any other study
investigating LY2603618 or any other checkpoint kinase one (Chk1) inhibitor

- Have known allergy to gemcitabine, pemetrexed, desipramine or LY2603618 or any
ingredient of gemcitabine, pemetrexed, desipramine or LY2603618 (like Captisol®)

- Have serious preexisting medical conditions (left to the discretion of the
investigator) other than advanced cancer

- Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not
required). Patients with treated CNS metastases are eligible for this study if they
are not currently receiving corticosteroids and/or anticonvulsants, and their disease
is asymptomatic and radiographically stable for at least 90 days.

- Have current hematologic malignancies or either acute or chronic leukemia

- Have an active fungal, bacterial, and/or known viral infection including human
immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not
required)

- Have QTc interval of >500 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 patient 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

- Patients who have an average weekly alcohol intake that exceeds 21 units per week
(males) and 14 units per week (females), or patients unwilling to stop alcohol
consumption for 24 hours before the study through the end of the study



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Cancer

Intervention(s)

Drug: Desipramine

Drug: Gemcitabine

Drug: LY2603618

Drug: Pemetrexed

Primary Outcome(s)

Plasma pharmacokinetics of Desipramine the area under the plasma concentration vs time curve from time zero to the last observed plasma concentration of drug (AUC0-tlast). [Time Frame: Period 1 and 2: predose,0.5,1,2,4,8,12,24,48,72,96,120,144 and 168 (period 2 only) hours post dose.]

Plasma pharmacokinetics of Desipramine the maximum concentration of the drug in the plasma after dosing (Cmax) [Time Frame: Periods 1 and 2: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 (period 2 only) hours post dose]

Plasma pharmacokinetics of Desipramine, the area under the plasma concentration vs time curve from time zero to infinity (AUC0-8) [Time Frame: Period 1 and 2:Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 (period 2 only) hours post dose]

Plasma pharmacokinetics of LY2603618 the area under the plasma concentration vs time curve from time zero to infinity (AUC0-8) [Time Frame: Period 2 only: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours post dose]

Plasma pharmacokinetics of LY2603618 the area under the plasma concentration vs time curve from time zero to the last observed plasma concentration of drug (AUC0-tlast) [Time Frame: Period 2 only: Predose 1,2,4,6,8,12,24,48,72,96,120,144 hours post dose.]

Plasma pharmacokinetics,of LY2603618 the maximum concentration of the drug in the plasma after dosing (Cmax) [Time Frame: Period 2 only: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours post dose]

Secondary Outcome(s)

Number of participants with a tumor response [Time Frame: Baseline to study completion (estimate of 20 months)]

Secondary ID(s)

13526

I2I-MC-JMMI

Source(s) of Monetary Support

Please refer to primary and secondary sponsors