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

cMET-dysregulated Advanced Solid Tumors Clinical Trial

Official title:

A Phase I, Multicenter, Open-label, Single-sequence Drug-drug Interaction Study to Assess the Effect of INC280 on the Pharmacokinetics of Digoxin and Rosuvastatin in Patients With cMET-dysregulated Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02626234
• Other study ID #: CINC280A2105
• Status: Completed
• Phase: Phase 1
• Start date: December 8, 2015
• Est. completion date: April 28, 2017

Study information

• Verified date: July 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: April 28, 2017
• Est. primary completion date: February 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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 Exclusion Criteria:

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. Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• cMET-dysregulated Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• INC280

• digoxin

• rosuvastatin

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Czechia	Novartis Investigative Site	Brno
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Ioannina	GR
Italy	Novartis Investigative Site	Bologna
Italy	Novartis Investigative Site	Candiolo	TO
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United States	Emory University School of Medicine/Winship Cancer Institute Phase 1 Working Group	Atlanta	Georgia
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Czechia,  Greece,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUClast of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Primary	AUCinf of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Primary	Lambda_z of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Primary	Cmax of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Primary	Tmax of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Primary	T1/2 of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Primary	CL/F of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Primary	Vz/F of digoxin and rosuvastatin	digoxin and rosuvastatin pharmacokinetics parameters	Up to 240 hours post digoxin and rosuvastatin dose
Secondary	Adverse events based on the CTCAE v4.03 grade (severity) and other safety data (e.g.,ECG, vital signs, laboratory results)	To assess safety and tolerability of INC280 in patients with cMET-dysregulated advanced solid tumors	From consent to 30 days post last dose
Secondary	Overall response rate of patients treated with INC280	Overall response rate is defined as Complete Response and Partial Response calculated per RECIST 1.1, per investigator assessment from Day 1 until date of progression or death whichever comes first	Up to 12 months
Secondary	Disease control rate of patients treated with INC280	Disease control rate is defined as calculated as the proportion of patients with best overall response of Complete Response, Partial Response, or Stable Disease calculated per RECIST 1.1, per investigator assessment from Day 1 until date of progression or death whichever comes first	Up to 12 months
Secondary	Concentration of INC280 during DDI phase	INC280 concentrations collected on Day 22 during DDI phase and Cycle 2 Day 1 during post DDI phase along with a listing of individual values.	Day 22, Cycle 2 Day 1

External Links

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