Chronic Kidney Disease (CKD)Phase 2LHW090NCT02678000
Study of the Safety, Tolerability, and Pharmacokinetics of LHW090 in Patients With Moderately Impaired Renal Function
A Phase 2 study testing LHW090 in people with Chronic Kidney Disease (CKD), run by Novartis Pharmaceuticals at 12 sites in 2 countries.
Trial summary
This was a randomized, double-blind, parallel group, placebo-controlled study, in two sequential parts that evaluated the renal safety, tolerability and pharmacokinetics of LHW090 in patients with moderately impaired renal function. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Chronic Kidney Disease (CKD)
- What is being tested?
- LHW090
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 10 Mar 2017to 11 Oct 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent must be obtained before any assessment is performed.
- Male and female patients, age 40 to 85 years of age (inclusive) on a stable (at least 1 month) dose of an angiotensin receptor blocker (ARB) and stable moderately impaired renal function, defined here as an eGFR 30-59 mL/min/1.73m^2 (inclusive) using the 4 variable MDRD Study equation for at least 3 months.
- At screening, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the patient has rested for at least five minutes, and again 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, 100-170 mm Hg
- diastolic blood pressure, 50-100 mm Hg
Show all 10Show fewer
- pulse rate, 50 - 95 bpm
- Patients should be excluded if their standing vital signs (relative to sitting) show findings which, in the opinion of the Investigator, are associated with clinical manifestation of postural hypotension (i.e. absence of any other cause). The Investigator should carefully consider enrolling patients with either a > 20 mm Hg decrease in systolic or a >10 mm Hg decrease in diastolic blood pressure, accompanied by a > 20 bpm increase in heart-rate (comparing standing to sitting results).
- Patients must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 38 kg/m^2. BMI = Body weight (kg) / [Height (m)]^2.
- Able to communicate well with the investigator, to understand and comply with the requirements of the study.
Who cannot join
- History of angioedema, drug-related or otherwise, as reported by the patient.
- Use of angiotensin converting enzyme inhibitors (ACE inhibitors), mineralocorticoid receptor antagonists (e.g. spironolactone or eplerenone), aliskiren, vasopressin receptor antagonists (e.g. tolvaptan), or oral alkalinizing agents (e.g. sodium and potassium citrate or Shohl's solution). Note: Patients who discontinue their ACE-inhibitor and substitute with an angiotensin receptor blocker (ARB) may be eligible to be rescreened provided their medication regimen has been stable for at least 1 month and their renal function has been stable for at least 3 months. Any substitutions or changes to a patient's medication regimen must be done under the guidance of the patient's treating physician.
- History of a renal transplant.
- Known current significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or significant severe valvular disease on prior or current echocardiogram.
- A serum potassium ≤ 3.5 mmol/l or ≥ 5.2 mmol/l at screening.
- A previous history or previously diagnosed renal cystic disease such as autosomal dominant polycystic kidney disease (history of an incidental asymptomatic acquired renal cyst(s) is excepted); obstructive uropathy; renal stone(s) in the past 2 years; chronic interstitial nephropathy; drug induced nephropathy; residual renal insufficiency following an episode of acute kidney injury or acute tubular necrosis related to renal atheroembolic disease, septic shock or ischemic nephropathy; renal tubular acidosis requiring treatment; nephrotic syndrome or nephrotic range proteinuria; or renal artery stenosis.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States7 sites
Novartis Investigative Site
Anaheim, California, 92801
Novartis Investigative Site
Lakewood, Colorado, 80228
Novartis Investigative Site
Miami Lakes, Florida, 33014
Novartis Investigative Site
Minneapolis, Minnesota, 55404
Novartis Investigative Site
New Orleans, Louisiana, 70119
Novartis Investigative Site
Orlando, Florida, 32810
Novartis Investigative Site
Saint Paul, Minnesota, 55114
Germany5 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Elsterwerda, 04910
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Hamburg, 22143
Novartis Investigative Site
Mannheim, 41061
About this study
Official title: A Two Part Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Renal Safety, Tolerability and Pharmacokinetics of LHW090 in Patients With Moderately Impaired Renal Function on Angiotensin Receptor Blockers
This was a randomized, double-blind, parallel group, placebo-controlled study, in two sequential parts that evaluated the renal safety, tolerability and pharmacokinetics of LHW090 in patients with moderately impaired renal function.
- Conditions
- Chronic Kidney Disease (CKD)
- Being tested
- LHW090, Placebo
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LHW090Drug
LHW090 is orally administered
PlaceboDrug
Matching placebo of LHW090
| Study group | Role | What they receive |
|---|---|---|
| LHW090 | Experimental | For Part 1, patients will receive 3 doses of LHW090 once daily with escalating doses every 4 days for a total 12 days of treatment.
For Part 2, patients will receive LHW090 once daily for 4 weeks. Receives: Drug: LHW090 |
| Placebo | Placebo comparator | For Part 1, patients will receive matching placebo once daily for 12 days. For Part 2, patients will receive matching placebo once daily for 4 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1)
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. For LHW090, incidence of AEs by primary organ class presented
Measured: Adverse events were collected from first dose of study treatment until end of study treatment, (12 days dosing period + 9 days follow up (PART 1) plus 30 days post treatment, up to maximum duration of approximately 20 months
Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' Where t is a Defined Time Point After Administration (AUC0-t) (PART 1)
The area under the plasma concentration-time curve from time zero to 24 hours. Area Under the Curve (AUC0-t) after 4 days dosing will be reported for PART 1. LHW090 and LHV527 (its active metabolite)
Measured: Within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs.
Number of Patients Who Developed a Renal Event (PART 2)
Patients who developed a renal event will be reported (defined as a ≥0.3 mg/dL increase in serum creatinine from baseline within 24-48 hours post dose )
Measured: Baseline, within 24 to 48 hours of post-dose weekly for up to 8 weeks
Secondary outcomes (3)
Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2)
The observed maximum plasma (or serum or blood) concentration following drug administration for PART 1 and PART 2
Measured: PART 1: within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs. PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing.
AUC0-t: Pharmacokinetics of LHW090/LHV527 (Active Metabolite)in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' Where t is a Defined Time Point After Administration (PART 2)
The area under the plasma concentration-time curve from time zero to 24 hours
Measured: PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing
Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2)
The time to reach the maximum concentration after drug administration
Measured: Part 1: within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs. Part 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2016 (estimated)
- Study start10 Mar 2017
- Primary completion11 Oct 2018
- Study completion11 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Kidney Disease (CKD)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02678000
- Sponsor's protocol ID
- CLHW090X2102
- Acronym
- LHW090
- Status last verified
- Oct 2021
- First submitted
- 29 Jan 2016
- Last updated
- 6 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Part Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Renal Safety, Tolerability and Pharmacokinetics of LHW090 in Patients With Moderately Impaired Renal Function on Angiotensin Receptor Blockers
- ClinicalTrials.gov ID
- NCT02678000
- Acronym / sponsor ID
- LHW090 / CLHW090X2102
- Conditions
- Chronic Kidney Disease (CKD)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 10 Mar 2017 (actual)
- Primary completion
- 11 Oct 2018 (actual)
- Study completion
- 11 Oct 2018 (actual)
- First posted
- 9 Feb 2016 (estimated)
- Results
- Posted 5 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a randomized, double-blind, parallel group, placebo-controlled study, in two sequential parts that evaluated the renal safety, tolerability and pharmacokinetics of LHW090 in patients with moderately impaired renal function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LHW090 | Experimental | Drug: LHW090For Part 1, patients will receive 3 doses of LHW090 once daily with escalating doses every 4 days for a total 12 days of treatment. For Part 2, patients will receive LHW090 once daily for 4 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboFor Part 1, patients will receive matching placebo once daily for 12 days. For Part 2, patients will receive matching placebo once daily for 4 weeks. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent must be obtained before any assessment is performed.
- Male and female patients, age 40 to 85 years of age (inclusive) on a stable (at least 1 month) dose of an angiotensin receptor blocker (ARB) and stable moderately impaired renal function, defined here as an eGFR 30-59 mL/min/1.73m^2 (inclusive) using the 4 variable MDRD Study equation for at least 3 months.
- At screening, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the patient has rested for at least five minutes, and again after three minutes in the standing position. Sitting vital signs should be within the following ranges:
- Patients should be excluded if their standing vital signs (relative to sitting) show findings which, in the opinion of the Investigator, are associated with clinical manifestation of postural hypotension (i.e. absence of any other cause). The Investigator should carefully consider enrolling patients with either a > 20 mm Hg decrease in systolic or a >10 mm Hg decrease in diastolic blood pressure, accompanied by a > 20 bpm increase in heart-rate (comparing standing to sitting results).
- Patients must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 38 kg/m^2. BMI = Body weight (kg) / [Height (m)]^2.
Key exclusion criteria (6 listed)
- History of angioedema, drug-related or otherwise, as reported by the patient.
- Use of angiotensin converting enzyme inhibitors (ACE inhibitors), mineralocorticoid receptor antagonists (e.g. spironolactone or eplerenone), aliskiren, vasopressin receptor antagonists (e.g. tolvaptan), or oral alkalinizing agents (e.g. sodium and potassium citrate or Shohl's solution). Note: Patients who discontinue their ACE-inhibitor and substitute with an angiotensin receptor blocker (ARB) may be eligible to be rescreened provided their medication regimen has been stable for at least 1 month and their renal function has been stable for at least 3 months. Any substitutions or changes to a patient's medication regimen must be done under the guidance of the patient's treating physician.
- History of a renal transplant.
- Known current significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or significant severe valvular disease on prior or current echocardiogram.
- A serum potassium ≤ 3.5 mmol/l or ≥ 5.2 mmol/l at screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LHW090LHW090 is orally administered | Drug | LHW090 |
| PlaceboMatching placebo of LHW090 | Drug | Placebo |
Primary outcome
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1)
Time frame: Adverse events were collected from first dose of study treatment until end of study treatment, (12 days dosing period + 9 days follow up (PART 1) plus 30 days post treatment, up to maximum duration of approximately 20 months
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. For LHW090, incidence of AEs by primary organ class presented
Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' Where t is a Defined Time Point After Administration (AUC0-t) (PART 1)
Time frame: Within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs.
The area under the plasma concentration-time curve from time zero to 24 hours. Area Under the Curve (AUC0-t) after 4 days dosing will be reported for PART 1. LHW090 and LHV527 (its active metabolite)
Number of Patients Who Developed a Renal Event (PART 2)
Time frame: Baseline, within 24 to 48 hours of post-dose weekly for up to 8 weeks
Patients who developed a renal event will be reported (defined as a ≥0.3 mg/dL increase in serum creatinine from baseline within 24-48 hours post dose )
3 secondary outcomes
Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2)
Time frame: PART 1: within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs. PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing.
AUC0-t: Pharmacokinetics of LHW090/LHV527 (Active Metabolite)in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' Where t is a Defined Time Point After Administration (PART 2)
Time frame: PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing
Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2)
Time frame: Part 1: within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs. Part 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LHW090 in people with Chronic Kidney Disease (CKD), run by Novartis Pharmaceuticals at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) (time frame: Adverse events were collected from first dose of study treatment until end of study treatment, (12 days dosing period + 9 days follow up (PART 1) plus 30 days post treatment, up to maximum duration of approximately 20 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2021.