An Ascending Dose Study to Assess Safety, Tolerability, PK/PD of LHW090 in Healthy Volunteers and in Subjects With Renal Dysfunction

NCT01846468 | Completed Phase 1

• 1 other identifier: CLHW090X2101
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the study is to provide pertinent information to enable decisions regarding the developability of LHW090 for use in patients with chronic renal insufficiency, including a comparison of the potential risk-benefit ratio of several doses of the study drug to enable optimal doses to be tested in later studies.

Conditions

Chronic Renal Insufficiency

Keywords

Healthy volunteers and patients,; renal insufficiency,

Outcome Measures

Primary Outcomes (3)

• Number of participants (Healthy Volunteers) with reported adverse events receiving single oral dose of LHW090 as assessment of safety and tolerabiility

  In this analysis AE and SAE will be reported

  6 months

• Number of participants (Healthy Volunteers) with reported adverse events receiving multiple oral dose of LHW090 as assessment of safety and tolerabiility

  In this analysis AE and SAE will be reported

  6 months

• Number of participants (patients) with reported adverse events receiving single oral dose of LHW090 as assessment of safety and tolerabiility

  In this analysis AE and SAE will be reported

  6 months

Secondary Outcomes (13)

• Pharmacokinetics of LHW090/LHV527 in plasma: observe maximum plasma concentration following LHW090 at steady state in healthy volunteers and patients

  Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs

• Pharmacokinetics of LHW090/LHV527 in plasma: time to reach the maximum concentration after administration of LHW090 (Tmax)

  Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs

• Pharmacokinetics of LHW090/LHV527 in plasma: area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (AUClast)

  Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs

• Pharmacokinetics of LHW090/LHV527 in plasma: area under the plasma concentration-time curve from time zero to infinity (AUCinf)

  Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs

• Pharmacokinetics of LHW090/LHV527 in plasma: terminal elimination half-life (T1/2)

  Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs

Study Arms (4)

Stage 1 : LHW090, Healthy Volunteers

EXPERIMENTAL

Healthy Volunteers will receive single dose of LHW090 on Day 1.

Drug: LHW090

Stage 2: LHW090, Healthy Volunteer

EXPERIMENTAL

Healthy Volunteers across 7 single ascending dose cohorts will be administered LHW090 or matching placebo day 1

Drug: LHW090; Drug: Placebo

Stage 3: LHW090, Healthy Volunteer

EXPERIMENTAL

Healthy Volunteers across 6 multiple ascending dose cohorts will be administered LHW090 or matching placebo for 14 days.

Drug: LHW090; Drug: Placebo

Stage 4: LHW090, Patients

EXPERIMENTAL

Subjects with Chronic Renal Insufficiency across 3 cohorts will be administered a single dose of LHW090 in Day 1.

Drug: LHW090

Interventions

LHW090 DRUG

1 mg, 12.5 mg, 100 mg capsules

Stage 1 : LHW090, Healthy Volunteers; Stage 2: LHW090, Healthy Volunteer; Stage 3: LHW090, Healthy Volunteer; Stage 4: LHW090, Patients

Placebo DRUG

Matching placebo capsules

Stage 2: LHW090, Healthy Volunteer; Stage 3: LHW090, Healthy Volunteer

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male and female subjects age 18 to 45 years of age included, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
• At screening, and first baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three minutes, and again (when required) after three minutes in the standing position. Sitting vital signs should be within the following ranges:
• oral body temperature between 35.0-37.5 °C systolic blood pressure, 90-140 mm Hg diastolic blood pressure, 50-90 mm Hg pulse rate, 40 - 90 bpm
• For Stage 4 subjects only:
• Male and female subjects, age 18 to 75 years of age included, with previously identified chronic renal insufficiency (estimated or measured GFR ≤ 45ml/min/1.73m2, or diabetic with estimated or measured GFR ≤ 60ml/min/1.73m2.) Diabetes can be established by the prescription and current use of anti-glycemic drugs, a random fasting glucose level of ≥ 144mg/dl or a hemoglobin A1c of ≥ 6.5%
• At screening, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three minutes, and again (when required) after three minutes in the standing position. Sitting vital signs should be within the following ranges:
• oral body temperature between 35.0-37.5 °C systolic blood pressure, 90-179 mm Hg diastolic blood pressure, 50-100 mm Hg pulse rate, 40 - 95 bpm

You may not qualify if:

• An active history of clinically significant ECG abnormalities as determined by the Investigator, or any of the following ECG abnormalities at Screening or Baseline:
• Long QT syndrome
• QTcF \> 450 msec (males; at screening)
• QTcF \> 460 msec (females; at screening)
• Known history of current clinically significant arrhythmias.
• Use of phosphodiesterase-5 inhibitors, UNLESS subjects agree to discontinue use of the drug for the duration of the study.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant
• Smokers (use of tobacco products in the previous 3 months). Urine cotinine levels will be measured during screening and at each baseline for all subjects. Smokers will be defined as any subject who reports tobacco use and/or who has a urine cotinine ≥ 500 ng/ml.
• Hemoglobin levels below 11.0 g/dl at screening.
• Subjects in Stage 3 only of the study will be excluded if they have any of the following:
• A history of allergy to topical anesthetic drops
• A history of corneal disease
• A history of eye surgery within three months prior to screening
• A history of corneal surgery (including refractive surgery and corneal transplantation)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Orlando, Florida, 32809, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37920, United States

Location

Related Links

• Results for CCLHW090X2101 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2013
• First Posted: May 3, 2013
• Study Start: March 1, 2013
• Primary Completion: June 28, 2014
• Study Completion: June 28, 2014
• Last Updated: December 17, 2020

Record last verified: 2017-02

Locations

US (2)