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Moxifloxacin

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Ramucirumab

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Active-control participants (first 16 participants) will receive one dose of moxifloxacin orally 7 days before the first treatment with ramucirumab. All participants will undergo triplicate electrocardiogram (ECG) tests (consisting of three individual ECGs performed consecutively within a period of 4 minutes) and vital signs at various times over the trial period.

For Cycle 1, all participants will also receive 2 infusions of diphenhydramine before ramucirumab therapy (the first infusion is 1 day before therapy and the second infusion is 15 minutes before therapy). For Cycles 2, 3, and 4, all participants will receive diphenhydramine 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, diphenhydramine infusions before ramucirumab therapy are at the investigator's discretion. Ramucirumab \[10 milligrams per kilogram (mg/kg)\] intravenously over 60 minutes, once every 3 weeks for minimum of 9 weeks without a break in between.

IMC-1121B (Ramucirumab) 10 mg/kg intravenously (IV) over 60 minutes, once every 3 weeks for minimum of 9 weeks.

IMC-1121B

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The purpose of this study is to determine if Ramucirumab (IMC-1121B) causes prolongation of the QT/QTc interval in participants with advanced cancer.

The primary purpose of this study is to determine if treatment with ramucirumab causes prolongation of the QTc/QT interval in participants with advanced cancer, to assess the safety and tolerability of ramucirumab therapy, and to evaluate the pharmacokinetic (PK) characteristics of ramucirumab

Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes

A Study to Evaluate the Relationship Between Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes in Patients With Advanced Cancer

All electrocardiogram (ECG) tests were performed in triplicate prior to ramucirumab treatment. QT is the interval between the Q and T waves and QTc is the QT corrected for heart rate using Fridericia's formula: QTc = QT/RR\^0.33 where RR is the interval between 2 R waves. Each participant's mean QT/QTc value was calculated for each ECG test during Cycle 3 and compared to his/her mean pretreatment QT/QTc value. The greatest change from baseline during Cycle 3 was reported. QTc prolongation is defined as a QTc exceeding 10 milliseconds (msec) with a lower 90% confidence interval (CI) exceeding 5 msec at any postdose time points per the International Conference on Harmonization (ICH) E14 guidelines for non-thorough QT studies (ICH 2005; ICH 2008). Least squares (LS) mean was calculated using a linear mixed model for repeated measures (MMRM) and adjusted for serum concentration.

Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.

Maximum observed concentration of IMC-1121B (ramucirumab) in serum during Cycle 1 (1 cycle=21 days).

Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.

Cmax was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.

The maximum observed serum concentration of IMC-1121B (ramucirumab) at steady state (Cmax,ss) during Cycle 3 (1 cycle=21 days).

The area under the concentration versus time curve from time 0 to infinity \[AUC(0-inf)\] is reported during Cycle 1 (1 cycle=21 days).

AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).

AUC was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.

The area under the concentration versus time curve over the dosing interval at steady state \[AUC(tau,ss)\] is reported during Cycle 3 (1 cycle=21 days).

Eli Lilly and Company

Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.

Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.

Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.

IMC-1121B (Ramucirumab)

Between 18 and 65 years

>=65 years

Age, Customized

Sex: Female, Male

White

Black

Asian

Race/Ethnicity, Customized

United States

Region of Enrollment

Hispanic or Latino

Non-Hispanic or Latino

Ethnicity

Safety population: Participants who received any quantity of ramucirumab, regardless of their eligibility for the study.

Chief Medical Officer

Participants who received a full study dose of ramucirumab in Cycle 3 and had at least 1 pretreatment ECG and postinfusion ECG at scheduled times as specified in the protocol.

Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants

Related TEAE

Related SAE

Related Grade 3 or higher TEAE

Related AE leading to discontinuation

Safety population: participants who received any quantity of ramucirumab, regardless of their eligibility for the study.

Number of Participants With Drug-Related Adverse Events (AEs)

Participants who received a full dose of ramucirumab and have evaluable Cmax data during Cycle 1.

Maximum Concentration (Cmax) During Cycle 1

Maximum Concentration (Cmax) During Cycle 1, Day 4

Maximum Concentration (Cmax) During Cycle 1, Day 8

Maximum Concentration (Cmax) During Cycle 1, Day 15

Maximum Concentration (Cmax) During Cycle 2

Participants who received a full dose of ramucirumab and have evaluable Cmax data during Cycle 3.

Maximum Concentration (Cmax) During Cycle 3

Participants who received a full dose of ramucirumab and have evaluable AUC data during Cycle 1.

Area Under Concentration (AUC) During Cycle 1

Area Under Concentration (AUC) During Cycle 1, Day 4

Area Under Concentration (AUC) During Cycle 1, Day 8

Area Under Concentration (AUC) During Cycle 1, Day 15

Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously over 1 hour, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.

Diphenhydramine: 25 to 50 milligrams (mg) administered intravenously 1 day before each administration of ramucirumab for Cycles 1 to 4. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.

Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.

Area Under Concentration (AUC) During Cycle 2, Day 1

Participants who received a full dose of ramucirumab and have evaluable AUC data during Cycle 3.

Spots Global Cancer Trial Database for Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes

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Study Description

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