Chronic Kidney Disease (CKD)
Conditions
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.
Interventions
DRUGLHW090
LHW090 is orally administered
DRUGPlacebo
Matching placebo of LHW090
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Germany, United States
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 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.
Participants by arm
| Arm | Count |
|---|---|
| LHW090 (PART 1) 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. | 7 |
| Placebo (PART 1) For Part 1, patients will receive matching placebo once daily for 12 days. | 4 |
| LHW090 100mg (PART 2) For PART 2, patients will receive LWH090 100 mg for 4 weeks | 28 |
| LHW090 200mg (PART 2) For PART 2, patients will receive LWH090 200 mg for 4 weeks | 27 |
| Placebo (PART 2) For Part 2, patients will receive matching placebo once daily for 4 weeks. | 18 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| PART 2 | Adverse Event | 0 | 0 | 2 | 1 | 0 |
| PART 2 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | LHW090 (PART 1) | Placebo (PART 1) | LHW090 100mg (PART 2) | LHW090 200mg (PART 2) | Placebo (PART 2) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 68.3 years STANDARD_DEVIATION 3.64 | 67.5 years STANDARD_DEVIATION 16.01 | 71.0 years STANDARD_DEVIATION 9.18 | 69.0 years STANDARD_DEVIATION 8.82 | 65.3 years STANDARD_DEVIATION 11.58 | 68.8 years STANDARD_DEVIATION 9.69 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 27 Participants | 24 Participants | 18 Participants | 78 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 8 Participants | 10 Participants | 9 Participants | 31 Participants |
| Sex: Female, Male Male | 6 Participants | 1 Participants | 20 Participants | 17 Participants | 9 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 4 | 0 / 28 | 0 / 27 | 0 / 18 |
| other Total, other adverse events | 1 / 7 | 0 / 7 | 1 / 7 | 2 / 4 | 13 / 28 | 16 / 27 | 9 / 18 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 4 | 3 / 28 | 0 / 27 | 0 / 18 |
Outcome results
Primary
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 )
Time frame: Baseline, within 24 to 48 hours of post-dose weekly for up to 8 weeks
Population: Safety Analysis Set -All subjects that received study drug and with no protocol deviations with relevant impact on safety
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LHW090 25 mg (PART 1) | Number of Patients Who Developed a Renal Event (PART 2) | 0 Participants |
| LHW090 50 mg (PART 1) | Number of Patients Who Developed a Renal Event (PART 2) | 1 Participants |
| LHW090 100 mg (PART 1) | Number of Patients Who Developed a Renal Event (PART 2) | 0 Participants |
Primary
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
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
Population: Safety Analysis Set -All subjects that received study drug and with no protocol deviations with relevant impact on safety
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LHW090 25 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Number of patients with at least one AE | 1 Count of Participants |
| LHW090 25 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Nervous system disorders | 0 Count of Participants |
| LHW090 25 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Musculoskeletal and connective tissue disorders | 0 Count of Participants |
| LHW090 25 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Gastrointestinal disorders | 1 Count of Participants |
| LHW090 25 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Psychiatric disorders | 0 Count of Participants |
| LHW090 25 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Skin and subcutaneous tissue disorders | 0 Count of Participants |
| LHW090 25 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | General disorders & administration site conditions | 0 Count of Participants |
| LHW090 50 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Nervous system disorders | 0 Count of Participants |
| LHW090 50 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | General disorders & administration site conditions | 0 Count of Participants |
| LHW090 50 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Skin and subcutaneous tissue disorders | 0 Count of Participants |
| LHW090 50 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Musculoskeletal and connective tissue disorders | 0 Count of Participants |
| LHW090 50 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Psychiatric disorders | 0 Count of Participants |
| LHW090 50 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Gastrointestinal disorders | 0 Count of Participants |
| LHW090 50 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Number of patients with at least one AE | 0 Count of Participants |
| LHW090 100 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | General disorders & administration site conditions | 0 Count of Participants |
| LHW090 100 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Number of patients with at least one AE | 1 Count of Participants |
| LHW090 100 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Gastrointestinal disorders | 1 Count of Participants |
| LHW090 100 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Skin and subcutaneous tissue disorders | 1 Count of Participants |
| LHW090 100 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Musculoskeletal and connective tissue disorders | 0 Count of Participants |
| LHW090 100 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Nervous system disorders | 0 Count of Participants |
| LHW090 100 mg (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Psychiatric disorders | 0 Count of Participants |
| Placebo (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Skin and subcutaneous tissue disorders | 2 Count of Participants |
| Placebo (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Psychiatric disorders | 1 Count of Participants |
| Placebo (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Nervous system disorders | 1 Count of Participants |
| Placebo (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Gastrointestinal disorders | 2 Count of Participants |
| Placebo (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Number of patients with at least one AE | 2 Count of Participants |
| Placebo (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | Musculoskeletal and connective tissue disorders | 1 Count of Participants |
| Placebo (PART 1) | Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) | General disorders & administration site conditions | 1 Count of Participants |
Primary
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)
Time frame: Within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LHW090 25 mg (PART 1) | 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) | 3750 h*ng/mL | Standard Deviation 815 |
| LHW090 50 mg (PART 1) | 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) | 7150 h*ng/mL | Standard Deviation 1480 |
| LHW090 100 mg (PART 1) | 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) | 13900 h*ng/mL | Standard Deviation 2180 |
| Placebo (PART 1) | 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) | 19200 h*ng/mL | Standard Deviation 3990 |
| LHW090/LHV527 50 mg (PART 1) | 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) | 36500 h*ng/mL | Standard Deviation 5720 |
| LHW090/LHV527 100 mg (PART 1) | 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) | 68800 h*ng/mL | Standard Deviation 11800 |
Secondary
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
Time frame: PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LHW090 25 mg (PART 1) | 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) | 21500 h* ng/mL | Standard Deviation 6810 |
| LHW090 50 mg (PART 1) | 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) | 42900 h* ng/mL | Standard Deviation 20700 |
| LHW090 100 mg (PART 1) | 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) | 96700 h* ng/mL | Standard Deviation 32800 |
| Placebo (PART 1) | 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) | 181000 h* ng/mL | Standard Deviation 51100 |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LHW090 25 mg (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 1160 ng / mL | Standard Deviation 589 |
| LHW090 25 mg (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 1690 ng / mL | Standard Deviation 338 |
| LHW090 50 mg (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 2000 ng / mL | Standard Deviation 1020 |
| LHW090 50 mg (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 3070 ng / mL | Standard Deviation 682 |
| LHW090 100 mg (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 4230 ng / mL | Standard Deviation 1400 |
| LHW090 100 mg (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 5100 ng / mL | Standard Deviation 734 |
| Placebo (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 6200 ng / mL | Standard Deviation 1560 |
| Placebo (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 4470 ng / mL | Standard Deviation 1690 |
| LHW090/LHV527 50 mg (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 7530 ng / mL | Standard Deviation 3750 |
| LHW090/LHV527 50 mg (PART 1) | Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 10300 ng / mL | Standard Deviation 1440 |
Secondary
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
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LHW090 25 mg (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 2.00 hour (hr) |
| LHW090 25 mg (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 3.58 hour (hr) |
| LHW090 50 mg (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 1.02 hour (hr) |
| LHW090 50 mg (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 4.00 hour (hr) |
| LHW090 100 mg (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 1.00 hour (hr) |
| LHW090 100 mg (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 4.00 hour (hr) |
| Placebo (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 3.00 hour (hr) |
| Placebo (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 2.00 hour (hr) |
| LHW090/LHV527 50 mg (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090 | 2.50 hour (hr) |
| LHW090/LHV527 50 mg (PART 1) | Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) | PK Value for LHW090/LHV527(active metabolite) | 4.00 hour (hr) |