Study of the Safety, Tolerability, and Pharmacokinetics of LHW090 in Patients With Moderately Impaired Renal Function
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02678000
Collaborator
(none)
84
12
2
19.1
7
0.4
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
84 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Mar 10, 2017
Actual Primary Completion Date
:
Oct 11, 2018
Actual Study Completion Date
:
Oct 11, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LHW090 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. |
Drug: LHW090
LHW090 is orally administered
|
| Placebo Comparator: Placebo 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. |
Drug: Placebo
Matching placebo of LHW090
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) [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) [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) [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 )
Secondary Outcome Measures
- Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) [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.]
The observed maximum plasma (or serum or blood) concentration following drug administration for PART 1 and PART 2
- 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) [PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing]
The area under the plasma concentration-time curve from time zero to 24 hours
- Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) [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]
The time to reach the maximum concentration after drug administration
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria (all Parts):
-
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
-
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.
Exclusion criteria:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Anaheim | California | United States | 92801 |
| 2 | Novartis Investigative Site | Lakewood | Colorado | United States | 80228 |
| 3 | Novartis Investigative Site | Miami Lakes | Florida | United States | 33014 |
| 4 | Novartis Investigative Site | Orlando | Florida | United States | 32810 |
| 5 | Novartis Investigative Site | New Orleans | Louisiana | United States | 70119 |
| 6 | Novartis Investigative Site | Minneapolis | Minnesota | United States | 55404 |
| 7 | Novartis Investigative Site | Saint Paul | Minnesota | United States | 55114 |
| 8 | Novartis Investigative Site | Berlin | Germany | 13353 | |
| 9 | Novartis Investigative Site | Elsterwerda | Germany | 04910 | |
| 10 | Novartis Investigative Site | Erlangen | Germany | 91054 | |
| 11 | Novartis Investigative Site | Hamburg | Germany | 22143 | |
| 12 | Novartis Investigative Site | Mannheim | Germany | 41061 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02678000
Other Study ID Numbers:
- CLHW090X2102
First Posted:
Feb 9, 2016
Last Update Posted:
Oct 6, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | All subjects (N=11) who enrolled in in PART 1 completed the study : LHW090 (N=7) and placebo (N=4). Of all subjects (N=73) in PART 2, a total of 69 subjects completed and 4 subjects discontinued. |
|---|---|
| Pre-assignment Detail | All subjects (N=11) who enrolled in in PART 1 completed the study : LHW090 (N=7) and placebo (N=4). Of all subjects (N=73) in PART 2, a total of 69 subjects completed and 4 subjects discontinued. |
| Arm/Group Title | LHW090 (PART 1) | Placebo (PART 1) | LHW090 100mg (PART 2) | LHW090 200mg (PART 2) | Placebo (PART 2) |
|---|---|---|---|---|---|
| Arm/Group Description | 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 1, patients will receive matching placebo once daily for 12 days. | For PART 2, patients will receive LWH090 100 mg for 4 weeks | For PART 2, patients will receive LWH090 200 mg for 4 weeks | For Part 2, patients will receive matching placebo once daily for 4 weeks. |
| Period Title: PART 1 | |||||
| STARTED | 7 | 4 | 0 | 0 | 0 |
| COMPLETED | 7 | 4 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
| Period Title: PART 1 | |||||
| STARTED | 0 | 0 | 28 | 27 | 18 |
| COMPLETED | 0 | 0 | 25 | 26 | 18 |
| NOT COMPLETED | 0 | 0 | 3 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | LHW090 (PART 1) | Placebo (PART 1) | LHW090 100mg (PART 2) | LHW090 200mg (PART 2) | Placebo (PART 2) | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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 1, patients will receive matching placebo once daily for 12 days. | For PART 2, patients will receive LWH090 100 mg for 4 weeks | For PART 2, patients will receive LWH090 200 mg for 4 weeks | For Part 2, patients will receive matching placebo once daily for 4 weeks. | Total of all reporting groups |
| Overall Participants | 7 | 4 | 28 | 27 | 18 | 84 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
68.3
(3.64)
|
67.5
(16.01)
|
71.0
(9.18)
|
69.0
(8.82)
|
65.3
(11.58)
|
68.8
(9.69)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
1
14.3%
|
3
75%
|
8
28.6%
|
10
37%
|
9
50%
|
31
36.9%
|
| Male |
6
85.7%
|
1
25%
|
20
71.4%
|
17
63%
|
9
50%
|
53
63.1%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
14.3%
|
1
25%
|
1
3.6%
|
3
11.1%
|
0
0%
|
6
7.1%
|
| White |
6
85.7%
|
3
75%
|
27
96.4%
|
24
88.9%
|
18
100%
|
78
92.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) |
|---|---|
| Description | 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 |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set -All subjects that received study drug and with no protocol deviations with relevant impact on safety |
| Arm/Group Title | LHW090 25 mg (PART 1) | LHW090 50 mg (PART 1) | LHW090 100 mg (PART 1) | Placebo (PART 1) |
|---|---|---|---|---|
| Arm/Group Description | For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive matching placebo once daily for 12 days. |
| Measure Participants | 7 | 7 | 7 | 4 |
| Number of patients with at least one AE |
1
14.3%
|
0
0%
|
1
3.6%
|
2
7.4%
|
| Gastrointestinal disorders |
1
14.3%
|
0
0%
|
1
3.6%
|
2
7.4%
|
| Skin and subcutaneous tissue disorders |
0
0%
|
0
0%
|
1
3.6%
|
2
7.4%
|
| General disorders & administration site conditions |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Musculoskeletal and connective tissue disorders |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Nervous system disorders |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Psychiatric disorders |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Title | 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) |
|---|---|
| Description | 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) |
| Time Frame | Within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set -Subjects with at least one available valid PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data |
| Arm/Group Title | LHW090 25 mg (PART 1) | LHW090 50 mg (PART 1) | LHW090 100 mg (PART 1) | LHW090/LHV527 25 mg (PART 1) | LHW090/LHV527 50 mg (PART 1) | LHW090/LHV527 100 mg (PART 1) |
|---|---|---|---|---|---|---|
| Arm/Group Description | For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527) | For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527) | For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527) |
| Measure Participants | 7 | 7 | 7 | 7 | 7 | 7 |
| Mean (Standard Deviation) [h*ng/mL] |
3750
(815)
|
7150
(1480)
|
13900
(2180)
|
19200
(3990)
|
36500
(5720)
|
68800
(11800)
|
| Title | Number of Patients Who Developed a Renal Event (PART 2) |
|---|---|
| Description | 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 ) |
| Time Frame | Baseline, within 24 to 48 hours of post-dose weekly for up to 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set -All subjects that received study drug and with no protocol deviations with relevant impact on safety |
| Arm/Group Title | LHW090 100mg (PART 2) | LHW090 200mg (PART 2) | Placebo (PART 2) |
|---|---|---|---|
| Arm/Group Description | For PART 2, patients will receive LWH090 100 mg once daily for 4 weeks | For PART 2, patients will receive LWH090 200 mg once daily for 4 weeks | For Part 2, patients will receive matching placebo once daily for 4 weeks. |
| Measure Participants | 28 | 27 | 18 |
| Count of Participants [Participants] |
0
0%
|
1
25%
|
0
0%
|
| Title | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) |
|---|---|
| Description | The observed maximum plasma (or serum or blood) concentration following drug administration for PART 1 and 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set - Subjects with at least one available valid PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data |
| Arm/Group Title | LHW090 25 mg (PART 1) | LHW090 50 mg (PART 1) | LHW090 100 mg (PART 1) | LHW090 100mg (PART 2) | LHW090 200mg (PART 2) |
|---|---|---|---|---|---|
| Arm/Group Description | For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment | For PART 2, patients will receive LWH090 100 mg once daily for 4 weeks | For PART 2, patients will receive LWH090 200 mg once daily for 4 weeks |
| Measure Participants | 7 | 7 | 7 | 7 | 7 |
| PK Value for LHW090 |
1160
(589)
|
2000
(1020)
|
4230
(1400)
|
4470
(1690)
|
7530
(3750)
|
| PK Value for LHW090/LHV527(active metabolite) |
1690
(338)
|
3070
(682)
|
5100
(734)
|
6200
(1560)
|
10300
(1440)
|
| Title | 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) |
|---|---|
| Description | The area under the plasma concentration-time curve from time zero to 24 hours |
| Time Frame | PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set -Subjects with at least one available valid PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data |
| Arm/Group Title | LHW090 100 mg (PART 2) | LHW090 200mg (PART 2) | LHW090/LHV527 100 mg (PART 2) | LHW090/LHV527 200 mg (PART 2) |
|---|---|---|---|---|
| Arm/Group Description | For PART 2, patients will receive LWH090 100 mg once daily for 4 weeks | For PART 2, patients will receive LWH090 200 mg once daily for 4 weeks | For PART 2, patients will receive LWH090 100 mg once daily for 4 weeks. (PK draw with active metabolite, LHV527) | For PART 2, patients will receive LWH090 200 mg once daily for 4 weeks. (PK draw with active metabolite, LHV527) |
| Measure Participants | 28 | 27 | 28 | 27 |
| Mean (Standard Deviation) [h* ng/mL] |
21500
(6810)
|
42900
(20700)
|
96700
(32800)
|
181000
(51100)
|
| Title | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) |
|---|---|
| Description | The time to reach the maximum concentration after drug administration |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set-Subjects with at least one available valid PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data |
| Arm/Group Title | LHW090 25 mg (PART 1) | LHW090 50 mg (PART 1) | LHW090 100 mg (PART 1) | LHW090 100mg (PART 2) | LHW090 200mg (PART 2) |
|---|---|---|---|---|---|
| Arm/Group Description | For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment | For PART 2, patients will receive LWH090 100 mg once daily for 4 weeks | For PART 2, patients will receive LWH090 200 mg once daily for 4 weeks |
| Measure Participants | 7 | 7 | 7 | 7 | 7 |
| PK Value for LHW090 |
2.00
|
1.02
|
1.00
|
2.00
|
2.50
|
| PK Value for LHW090/LHV527(active metabolite) |
3.58
|
4.00
|
4.00
|
3.00
|
4.00
|
Adverse Events
| Time Frame | Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. | |||||||||||||
| Arm/Group Title | LHW090 25 mg (PART 1) | LHW090 50 mg (PART 1) | LHW090 100 mg (PART 1) | PART 1 Placebo | LHW090 100mg (PART 2) | LHW090 200 mg (PART 2) | Placebo (PART 2 | |||||||
| Arm/Group Description | For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. | For Part 1, patients will receive matching placebo once daily for 12 days. | For PART 2, patients will receive LWH090 100 mg once daily for 4 weeks | For PART 2, patients will receive LWH090 200 mg once daily for 4 weeks | For Part 2, patients will receive matching placebo once daily for 4 weeks. | |||||||
All Cause Mortality |
||||||||||||||
| LHW090 25 mg (PART 1) | LHW090 50 mg (PART 1) | LHW090 100 mg (PART 1) | PART 1 Placebo | LHW090 100mg (PART 2) | LHW090 200 mg (PART 2) | Placebo (PART 2 | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 0/27 (0%) | 0/18 (0%) | |||||||
Serious Adverse Events |
||||||||||||||
| LHW090 25 mg (PART 1) | LHW090 50 mg (PART 1) | LHW090 100 mg (PART 1) | PART 1 Placebo | LHW090 100mg (PART 2) | LHW090 200 mg (PART 2) | Placebo (PART 2 | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 3/28 (10.7%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Radius fracture | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Skin laceration | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Angioedema | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| LHW090 25 mg (PART 1) | LHW090 50 mg (PART 1) | LHW090 100 mg (PART 1) | PART 1 Placebo | LHW090 100mg (PART 2) | LHW090 200 mg (PART 2) | Placebo (PART 2 | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/7 (14.3%) | 0/7 (0%) | 1/7 (14.3%) | 2/4 (50%) | 13/28 (46.4%) | 16/27 (59.3%) | 9/18 (50%) | |||||||
| Ear and labyrinth disorders | ||||||||||||||
| Vertigo | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Eye disorders | ||||||||||||||
| Eye pruritus | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Lacrimation increased | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Abdominal discomfort | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 0/27 (0%) | 1/18 (5.6%) | |||||||
| Diarrhoea | 1/7 (14.3%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 2/28 (7.1%) | 4/27 (14.8%) | 1/18 (5.6%) | |||||||
| Dry mouth | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/4 (25%) | 0/28 (0%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Dyspepsia | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 1/18 (5.6%) | |||||||
| Faeces discoloured | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/4 (25%) | 0/28 (0%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Frequent bowel movements | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Nausea | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| General disorders | ||||||||||||||
| Chest discomfort | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Fatigue | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 2/28 (7.1%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Infusion site haemorrhage | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/4 (25%) | 0/28 (0%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Oedema peripheral | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 2/18 (11.1%) | |||||||
| Pyrexia | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 0/27 (0%) | 1/18 (5.6%) | |||||||
| Xerosis | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 0/27 (0%) | 1/18 (5.6%) | |||||||
| Immune system disorders | ||||||||||||||
| Hypersensitivity | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Gastrointestinal infection | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Nasopharyngitis | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 1/18 (5.6%) | |||||||
| Rhinitis | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Urinary tract infection | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Viral upper respiratory tract infection | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Investigations | ||||||||||||||
| Blood creatinine increased | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 1/18 (5.6%) | |||||||
| Blood pressure decreased | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 2/27 (7.4%) | 0/18 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Gout | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Hyperkalaemia | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Lactose intolerance | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 0/27 (0%) | 1/18 (5.6%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Arthralgia | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 0/27 (0%) | 1/18 (5.6%) | |||||||
| Back pain | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Muscle spasms | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/4 (25%) | 0/28 (0%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Lipoma | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Dizziness | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Headache | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/4 (25%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Abnormal dreams | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/4 (25%) | 0/28 (0%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Apathy | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Insomnia | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Sleep disorder | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 2/27 (7.4%) | 0/18 (0%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Dysuria | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Haematuria | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 0/27 (0%) | 1/18 (5.6%) | |||||||
| Pollakiuria | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Dyspnoea | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Epistaxis | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 0/27 (0%) | 1/18 (5.6%) | |||||||
| Nasal dryness | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Nasal pruritus | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 4/27 (14.8%) | 0/18 (0%) | |||||||
| Oropharyngeal pain | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Rhinorrhoea | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 1/18 (5.6%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Acne | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Alopecia | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/4 (25%) | 0/28 (0%) | 0/27 (0%) | 0/18 (0%) | |||||||
| Drug eruption | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Ecchymosis | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/4 (25%) | 0/28 (0%) | 0/27 (0%) | 1/18 (5.6%) | |||||||
| Pruritus | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/4 (0%) | 6/28 (21.4%) | 1/27 (3.7%) | 1/18 (5.6%) | |||||||
| Pruritus generalised | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 2/27 (7.4%) | 0/18 (0%) | |||||||
| Rash macular | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 0/28 (0%) | 1/27 (3.7%) | 0/18 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Haematoma | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 1/28 (3.6%) | 0/27 (0%) | 1/18 (5.6%) | |||||||
| Hypotension | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/4 (0%) | 2/28 (7.1%) | 2/27 (7.4%) | 0/18 (0%) | |||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| Novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02678000
Other Study ID Numbers:
- CLHW090X2102
First Posted:
Feb 9, 2016
Last Update Posted:
Oct 6, 2021
Last Verified:
Oct 1, 2021