| CTRI Number |
CTRI/2025/05/087526 [Registered on: 23/05/2025] Trial Registered Prospectively |
| Last Modified On: |
06/03/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Other |
|
Public Title of Study
|
This study is to check the Drug-drug interaction of LXE408 with itraconazole and phenytoin |
|
Scientific Title of Study
|
A Phase I, open-label, single-sequence, two-part, two-period, drug-drug interaction study to assess the effect of itraconazole and phenytoin on the pharmacokinetics of a single oral dose of LXE408 in healthy participants |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CLXE408A12105 v01 Dated 31-Jan-2025 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Murugananthan K |
| Designation |
SSO Country Head |
| Affiliation |
Novartis Healthcare Private Limited |
| Address |
Novartis Healthcare Private Limited 7 floor Inspire BKC G Block BKC
Main Road Bandra Kurla Complex Bandra (East) Mumbai Mumbai
MAHARASHTRA 400051 India
Mumbai
MAHARASHTRA
400051
India
Mumbai
MAHARASHTRA
400051
India |
| Phone |
912250243544 |
| Fax |
|
| Email |
murugananthan.k@novartis.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Murugananthan K |
| Designation |
SSO Country Head |
| Affiliation |
Novartis Healthcare Private Limited |
| Address |
Novartis Healthcare Private Limited 7 floor Inspire BKC G Block BKC
Main Road Bandra Kurla Complex Bandra (East) Mumbai Mumbai
MAHARASHTRA 400051 India
Mumbai
MAHARASHTRA
400051
India
Mumbai
MAHARASHTRA
400051
India |
| Phone |
912250243544 |
| Fax |
|
| Email |
murugananthan.k@novartis.com |
|
Details of Contact Person
Public Query
|
| Name |
Murugananthan K |
| Designation |
SSO Country Head |
| Affiliation |
Novartis Healthcare Private Limited |
| Address |
Novartis Healthcare Private Limited 7 floor Inspire BKC G Block BKC
Main Road Bandra Kurla Complex Bandra (East) Mumbai Mumbai
MAHARASHTRA 400051 India
Mumbai
MAHARASHTRA
400051
India
Mumbai
MAHARASHTRA
400051
India |
| Phone |
912250243544 |
| Fax |
|
| Email |
murugananthan.k@novartis.com |
|
|
Source of Monetary or Material Support
|
| Novartis Pharma AG, Novartis Campus 4056 - Basel, Switzerland |
|
|
Primary Sponsor
|
| Name |
Novartis Healthcare Pvt Ltd |
| Address |
7 floor, Inspire BKC, G Block, BKC Main Road, Bandra Kurla
Complex, Bandra (East), Mumbai - 400051,lndia |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Darshankumar Kharadi |
Veeda Clinical Research Limited |
1st, 2nd , 3rd & 4th floor, Vedant Complex, Near Y.M.C.A. Club, S.G. Highway Road, Vejalpur, Ahmedabad-380051, Gujarat, India
Ahmadabad
GUJARAT |
9925605916
darshankumar.k3015@veedacr.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Sangini Hospital Ethics Committee, Sangini Hospital, Santorini Square, B/H Abhishree Complex, Opp. Star Bazar, Nr Jodhpur Cross Roads, Satellite, Ahmedabad, Gujarat - 380015, India |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Healthy Human Volunteers |
Drug-drug interaction study of single oral dose of LXE408 with itraconazole and phenytoin |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Itraconazole |
200 mg itraconazole once daily from Day 7 to Day 20 with breakfast except on Day 10 when LXE408 is given concomitantly under fasting condition |
| Intervention |
LXE408 |
Single 50mg oral dose on day 1 |
| Comparator Agent |
NA |
NA |
| Intervention |
Phenytoin |
oral doses of 100 mg phenytoin three-times daily on
Day 7 through Day 25 |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
55.00 Year(s) |
| Gender |
Both |
| Details |
1.Subjects willing to adhere to the protocol requirements and to provide written informed consent prior to participation in the study.
2.Healthy male or non-childbearing potential female participants 18 to 55 years of age inclusive at screening.
3.In good health as determined by no clinically significant findings from past medical history, physical examination, vital signs, chest X-rays, 2D-ECHO, ECG, and clinical laboratory tests during screening and/or baseline.
4.Participants must weigh at least 50.0 kg with a body mass index (BMI) within the range of 18.0 to 29.9 kg/m2, inclusive, at screening.
5.At screening and baseline, vital signs (systolic and diastolic blood pressure, body temperature and pulse rate) will be assessed in the sitting position and again (when required) in the standing position. Vital signs after sitting 3 minutes in a quiet environment must be within the following ranges: oral body temperature between 35.0-37.5°C, systolic blood pressure between 90-139 mm Hg, diastolic blood pressure between 50-89 mm Hg, and pulse rate between 50-100 bpm.
|
|
| ExclusionCriteria |
| Details |
1.History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants.
2.Participants who have received other investigational drugs within 5 half-lives or within 30 days or until the expected pharmacodynamic effect has returned to baseline prior to initial dosing, whichever is longer.
3.History of hypersensitivity to the investigational compounds (LXE408, Itraconazole or Phenytoin)/compound class or excipients being used in this study
4.Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 30 days after stopping study treatment.
5.Any single parameter of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) exceeding 1.2 × upper limit of normal (ULN) and ≥ 1.5 × ULN total bilirubin OR any elevation above ULN of more than one parameter of ALT, AST, GGT, ALP, or serum bilirubin at screening
6.Any single parameter of amylase or lipase above 1.0 x ULN, or any history or presence of clinical symptoms suggestive of pancreatitis.
7.History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine (creatinine level above 1.5x ULN) or blood urea, or abnormal urinary constituents (e.g. proteinuria, microscopy confirmed hematuria) at screening.
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
To investigate the effect of multiple doses of CYP3A inhibitor, itraconazole, at 200 mg QD on the PK of a single 50 mg oral dose of LXE408 in healthy participants.
To investigate the effect of multiple doses of CYP3A inducer, phenytoin, at 100 mg TID on the PK of a single 50 mg oral dose of LXE408 in healthy participants
|
Primary PK parameters of LXE408 in plasma such as AUClast, AUCinf, AUC0-t (as appropriate), Cmax and Tmax.
Secondary plasma PK parameters of LXE408 including AUC0-24, CL/F, Vz/F and T1/2 as feasible.
[Part 1 & Part 2 in Period 1: From dose (0h) up to 120h.
Part 1 in Period 2: From Pre-dose (0h) up to 264h.
Part 2 in Period 2: From Pre-dose (0h) up to 120h.]
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To assess the safety & tolerability of a single 50 mg oral dose of LXE408 given alone & with multiple doses of itraconazole at 200 mg QD in healthy participants.
To assess the safety & tolerability of a single 50 mg oral dose of LXE408 given alone & with multiple 100 mg doses of phenytoin TID in healthy participants. |
All safety endpoints including vital signs, ECG, clinical laboratory evaluation & AEs [from Screening to End of Study]
|
|
|
Target Sample Size
|
Total Sample Size="40"
Sample Size from India="40"
Final Enrollment numbers achieved (Total)= "40"
Final Enrollment numbers achieved (India)="40" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
11/06/2025 |
| Date of Study Completion (India) |
19/12/2025 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="2"
Days="20" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
The purpose of this study is to evaluate the effect of co-administration of itraconazole, a strong cytochrome P450 CYP3A inhibitor, or co-administration of phenytoin, a strong CYP3A inducer on the pharmacokinetics (PK) of a single 50mg dose of LXE408. In addition, the safety and tolerability of a single dose of LXE408 with or without the co-administration of itraconazole or phenytoin will be evaluated. The study will be conducted in healthy participants. type of the treatment is oral drug administration and study type is interventional study. This study is an open-label, single-sequence, two-part, two-period, crossover drug-drug interaction (DDI) study designed to evaluate the PK of a single-dose of 50 mg LXE408 in healthy participants when given alone and during multiple dosing of 200 mg itraconazole QD (Part 1) or phenytoin 100 mg TID (Part 2). The study consists of 2 separate and independent parts, Part 1 and Part 2, with 2 separate groups of participants enrolled. Each of the 2 study parts comprises a screening period of up to 28 days, a baseline evaluation (on Day -1 of Period 1) and 2 treatment periods. Participants who meet the eligibility criteria at the screening and baseline assessments on Day-1 of Period 1 will be admitted to the study site and will remain domiciled until the Study Completion (End of Study, EOS). A participant will be enrolled in either of the parts.
Approximately 20 male or female participants 18 to 55 years of age will be enrolled and dosed with the aim to have at least 16 evaluable participants in each part. Additional participants may be enrolled if participants discontinue from the study for reasons other than safety. |