Pharmacokinetic (PK) and Safety Study of Iptacopan (LNP023) in Participants With Mild, Moderate, and Severe Hepatic Impairment Compared to Matched Control Healthy Participants With Normal Hepatic Function.

A Phase 1, Single Dose, Open-label Study to Investigate the Pharmacokinetics and Safety of Iptacopan (LNP023) in Participants With Mild, Moderate, and Severe Hepatic Impairment Compared to Matched Control Healthy Participants With Normal Hepatic Function

This was an open-label, single dose parallel group study to evaluate the PK of iptacopan in participants with mild, moderate, and severe hepatic impairment compared to matched healthy control participants.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Iptacopan; Drug: Iptacopan

Detailed Description

The study comprised of a screening period up to 28 days, one Baseline evaluation on Day -1, a single dose administration of 200 mg of iptacopan followed by PK sampling to 240 hr, and an End-of-Study (EOS) visit (Day 11). All participants had a post study safety follow-up call conducted approximately 30 days after last administration of study drug.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78215
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants eligible for inclusion in this study met the following key criteria:

• Written informed consent was obtained before performing any assessment.
• Male participants and female participants of non-childbearing potential 18 to 75 years of age (inclusive).
• Participants were to weigh at least 55 kg to participate in the study and were to have a body mass index (BMI) within the range of 18 to 35 kg/m2 for healthy participants.

For hepatic impairment participants without overt ascites, the BMI was to be within the range of 18 to 40 kg/m2. For hepatic impairment participants with overt ascites, the BMI was to be within the range of 18 to 45 kg/m2.

• Ability to communicate well with the Investigator, to understand and comply with the requirements of the study.
• Participant was willing to remain in the clinical research unit as required by the protocol

Exclusion Criteria:

Participants meeting any of the following criteria were excluded from this study:

• Use of other investigational drugs within the last 30 days or 5 half-lives prior to dosing, whichever was longer.
• History of hypersensitivity to the investigational compound/compound class or its excipients being used in this study.
• Pregnant or nursing (lactating) women. Pregnancy was defined as the state of a female after conception and until termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
• Known history of, or current clinically significant arrhythmias, history of prolonged QT correction formula (QTcF) interval or QTcF > 450 msec (males) or QTcF > 460 msec (females) at screening in healthy participants and history of prolonged QTcF interval or QTcF > 470 msec (males) or QTcF > 480 msec (females) at screening in participants with hepatic impairment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy participants; Iptacopan 200 mg single dose	Drug: Iptacopan; Single oral dose of iptacopan 200 mg oral capsules; Other Names: LNP023; Drug: Iptacopan; Single oral dose of Iptacopan 200 mg oral capsules; Other Names: LNP023
Experimental: Mild hepatic impairment patients; Iptacopan 200 mg single dose	Drug: Iptacopan; Single oral dose of iptacopan 200 mg oral capsules; Other Names: LNP023; Drug: Iptacopan; Single oral dose of Iptacopan 200 mg oral capsules; Other Names: LNP023
Experimental: Moderate hepatic impairment patients; Iptacopan 200 mg single dose	Drug: Iptacopan; Single oral dose of iptacopan 200 mg oral capsules; Other Names: LNP023; Drug: Iptacopan; Single oral dose of Iptacopan 200 mg oral capsules; Other Names: LNP023
Experimental: Severe hepatic impairment patients; Iptacopan 200 mg single dose	Drug: Iptacopan; Single oral dose of iptacopan 200 mg oral capsules; Other Names: LNP023; Drug: Iptacopan; Single oral dose of Iptacopan 200 mg oral capsules; Other Names: LNP023

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters of iptacopan: Cmax The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1)	To assess the PK properties of iptacopan after a single oral dose of 200 mg in participants with mild, moderate, or severe hepatic impairment as compared to matched healthy participants with normal hepatic function (Child-Pugh classification).	Day 1 (few time points), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10 and Day 11
Pharmacokinetics parameters of iptacopan: Tmax The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)	To assess the PK properties of iptacopan after a single oral dose of 200 mg in participants with mild, moderate, or severe hepatic impairment as compared to matched healthy participants with normal hepatic function (Child-Pugh classification).	Day 1 (few time pints), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10 and Day 11
Pharmacokinetic parameters of iptacopan: AUClast The AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time × volume-1)	To assess the PK properties of iptacopan after a single oral dose of 200 mg in participants with mild, moderate, or severe hepatic impairment as compared to matched healthy participants with normal hepatic function (Child-Pugh classification).	Day 1 (few time points), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10 and Day 11
Pharmacokinetics parameters of iptacopan: AUCinf The AUC from time zero to infinity (mass × time × volume-1)	to assess the PK properties of iptacopan after a single oral dose of 200 mg in participants with mild, moderate, or severe hepatic impairment as compared to matched healthy participants with normal hepatic function (Child-Pugh classification).	Day 1 (few time points), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10 and Day 11

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novctrd.com.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Actual): June 20, 2022
• Study Completion (Actual): June 20, 2022

Study Registration Dates

• First Submitted: October 13, 2021
• First Submitted That Met QC Criteria: October 13, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: hepatic impairment; single-dose; LNP023; iptacopan
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CLNP023A2105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No