A Drug-drug Interaction (DDI) Study to Assess the Effect of INC280 on the Pharmacokinetics of Digoxin and Rosuvastatin in Patients With cMET-dysregulated Advanced Solid Tumors

NCT02626234 | Completed Phase 1 FDA Drug

• 1 other identifier: CINC280A2105
• Study Type: interventional
• Target: 32
• Locations: 8 countries
• Sites: 15

Brief Summary

the study aim to assess the effect of INC280 on the pharmacokinetics of digoxin and rosuvastatin in patients with cMET-dysregulated advanced solid tumors

Conditions

cMET-dysregulated Advanced Solid Tumors

Keywords

cMET, INC280, rosuvastatin, digoxin

Outcome Measures

Primary Outcomes (8)

• AUClast of digoxin and rosuvastatin

  digoxin and rosuvastatin pharmacokinetics parameters

  Up to 240 hours post digoxin and rosuvastatin dose

• AUCinf of digoxin and rosuvastatin

  digoxin and rosuvastatin pharmacokinetics parameters

  Up to 240 hours post digoxin and rosuvastatin dose

• Lambda_z of digoxin and rosuvastatin

  digoxin and rosuvastatin pharmacokinetics parameters

  Up to 240 hours post digoxin and rosuvastatin dose

• Cmax of digoxin and rosuvastatin

  digoxin and rosuvastatin pharmacokinetics parameters

  Up to 240 hours post digoxin and rosuvastatin dose

• Tmax of digoxin and rosuvastatin

  digoxin and rosuvastatin pharmacokinetics parameters

  Up to 240 hours post digoxin and rosuvastatin dose

• T1/2 of digoxin and rosuvastatin

  digoxin and rosuvastatin pharmacokinetics parameters

  Up to 240 hours post digoxin and rosuvastatin dose

• CL/F of digoxin and rosuvastatin

  digoxin and rosuvastatin pharmacokinetics parameters

  Up to 240 hours post digoxin and rosuvastatin dose

• Vz/F of digoxin and rosuvastatin

  digoxin and rosuvastatin pharmacokinetics parameters

  Up to 240 hours post digoxin and rosuvastatin dose

Secondary Outcomes (4)

• Adverse events based on the CTCAE v4.03 grade (severity) and other safety data (e.g.,ECG, vital signs, laboratory results)

  From consent to 30 days post last dose

• Overall response rate of patients treated with INC280

  Up to 12 months

• Disease control rate of patients treated with INC280

  Up to 12 months

• Concentration of INC280 during DDI phase

  Day 22, Cycle 2 Day 1

Study Arms (1)

INC280

EXPERIMENTAL

Drug: INC280; Drug: digoxin; Drug: rosuvastatin

Interventions

INC280 DRUG

INC280

digoxin DRUG

INC280

rosuvastatin DRUG

INC280

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have:
• advanced solid tumors and have confirmed cMET dysregulation
• at least one measurable lesion as defined by RECIST 1.1.
• recovered from all toxicities related to prior anti-cancer therapies
• adequate organ function
• ECOG performance status (PS) of 0 or 1

You may not qualify if:

• Patients must not have:
• known hypersensitivity to any of the excipients of INC280
• prior treatment with cMET or HGF-targeting inhibitor
• known hypersensitivity to digoxin or rosuvastatin or its excipients
• symptomatic central nervous system (CNS) metastases who are neurologically unstable
• presence or history of carcinomatous meningitis
• history of another primary malignancy that is currently clinically significant or currently requires active intervention
• Clinically significant, uncontrolled heart diseases, including QTcF ≥ 450 msec (male patients), ≥ 460 msec (female patients) on the screening ECG
• Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting INC280
• Major surgery within 4 weeks prior to starting INC280
• Patients receiving unstable or increasing doses of corticosteroids.
• Impairment of GI function or GI disease that may significantly alter the absorption of INC280
• Patients who have received, or are expected to receive digoxin or rosuvastatin within 21 days prior to the beginning of the DDI phase (Day 1) and for the duration of the DDI phase.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Emory University School of Medicine/Winship Cancer Institute Phase 1 Working Group

Atlanta, Georgia, 30322, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Novartis Investigative Site

Vienna, A-1090, Austria

Location

Novartis Investigative Site

Edegem, Antwerpen, 2650, Belgium

Location

Novartis Investigative Site

Brno, 65653, Czechia

Location

Novartis Investigative Site

Ioannina, GR, 455 00, Greece

Location

Novartis Investigative Site

Athens, 18547, Greece

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Candiolo, TO, 10060, Italy

Location

Novartis Investigative Site

Bologna, 40138, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28222, Spain

Location

Novartis Investigative Site

London, W1G 6AD, United Kingdom

Location

Novartis Investigative Site

Manchester, M20 9BX, United Kingdom

Location

Related Links

• Results for CINC280A2105 can be found Novartis Clinical trials results website

MeSH Terms

Interventions

capmatinib; Digoxin; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: December 10, 2015
• Study Start: December 8, 2015
• Primary Completion: February 28, 2017
• Study Completion: April 28, 2017
• Last Updated: December 10, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); US (2); BE (1); AU (1); ES (2); IT (4); GR (2); GB (2)