A Multi-Center, Open-Label Study

NCT01468259 | Withdrawn Phase 1

• 1 other identifier: Droxidopa NOH103
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be an open-label, single-treatment, single-dose, parallel group study to evaluate the pharmacokinetics (PK) of droxidopa in subjects with mild, moderate, and severe renal dysfunction and End Stage Renal Disease (ESRD) after a single dose compared to matched healthy subjects with normal renal function. A total of 48 male or female subjects, 16 subjects with normal renal function (eGFR greater than 90 mL/min/1.73m²) and eight each (8) with mild (60 less than eGFR less than 89 mL/min/1.73m²), moderate (30 less than eGFR less than 59 mL/min/1.73m²), or severe (15 less than eGFR less than 29 mL/min/1.73m²) renal impairment or ESRD (eGFR \< 15 mL/min/1.73m² and requiring hemodialysis) will be selected according to the inclusion and exclusion criteria. The medical and laboratory examinations will take place within 28 days before dosing. A single dose of 600 mg of droxidopa as an investigational drug will be administered with 240 mL of water after an overnight fast (minimum 10 hours). Blood samples for the measurement of plasma concentrations of droxidopa and metabolites including but not limited to 3-OM-DOPS, NE, vanillic acid, and protocatechuic acid will be collected before and 0, .5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36 hours after dosing for healthy volunteers and subjects with mild, moderate, and severe renal impairment and those with ESRD. For the latter, samples will be collected on both a non-hemodialysis and a hemodialysis visit. During dialysis, samples of dialysate, from the arterial and venous sides of the dialyzer will be collected at 30-minute intervals during the dialysis period. In addition, the entire dialysate will be collected, its volume recorded, and a sample retained for the measurement of droxidopa and metabolites including but not limited to 3-OM-DOPS, NE, vanillic acid, and protocatechuic acid concentrations. Urine samples for the measurement of urinary excretion of droxidopa and metabolites including but not limited to 3-OM-DOPS, NE, vanillic acid, and protocatechuic acid will be collected before and over the following intervals after dosing: 0 2, 2-4, 4-6, 6-8, 8-12, 12-24, and 24-36 hours for healthy volunteers and subjects with mild, moderate, and severe renal impairment. A post-study visit with physical examination and laboratory tests will take place within seven (7) days after the last PK blood sampling.

Conditions

Renal Disease; End Stage Renal Disease

Outcome Measures

Primary Outcomes (1)

• Primary Objective Pharmacokinetic profile

  The primary objective of this study is to evaluate the pharmacokinetics (PK) of droxidopa in subjects with mild, moderate, and severe renal dysfunction and ESRD after a single oral dose compared to matched healthy subjects with normal renal function. The PK parameters Cmax, Tmax, AUC(inf), CL/F, Vz/F, t½, and CLr are considered the primary parameters for evaluation.

  before and 0, .5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36 hours

Secondary Outcomes (1)

• Secondary Objective Safety and tolerability

  before and 0, .5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36 hours

Study Arms (5)

Normal renal function

EXPERIMENTAL

16 subjects with normal renal function (eGFR greater than 90 mL/min/1.73m²)

Drug: Droxidopa

Mild RD

EXPERIMENTAL

Eight (8) with mild (60 less than eGFR less than 89 mL/min/1.73m²)

Drug: Droxidopa

Moderate RD

EXPERIMENTAL

Eight with moderate (30 less than eGFR less than 59 mL/min/1.73m²),

Drug: Droxidopa

Severe RD

EXPERIMENTAL

Eight with severe (15 less than eGFR less than 29 mL/min/1.73m²)

Drug: Droxidopa

End Stage Renal Disease

EXPERIMENTAL

Eight with ESRD (eGFR \< 15 mL/min/1.73m² and requiring hemodialysis)

Drug: Droxidopa

Interventions

Droxidopa DRUG

The dose to be used is a single 600 mg dose (2 x 300 mg capsules) of droxidopa.

End Stage Renal Disease; Mild RD; Moderate RD; Normal renal function; Severe RD

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent
• Male or Female between 18 and 79 years
• Female subject of childbearing potential not surgically sterile or min 2 years postmenopausal must use approved contraceptives
• BMI 20 to 40 kg per m2
• Refrain from exercise
• eGFR per protocol for condition
• Sufficient venous access
• Stable medication dosing 14 days prior to and during study
• Healthy control subjects must show good general health per protocol
• Subjects will be matched Healthy to Renal Impaired by demographics data

You may not qualify if:

• Inability to complete study
• Insufficient venous access
• Clinically significant illness within 4 weeks of study
• History of clinically unstable disease except renal impairment in those subjects
• Medical or surgical conditions that may inhibit absorption of IP
• Laboratory value or medical issue which may interfere with study data or be hazardous for the subject
• Medication that may interfere with drug absorption or elimination process 4 weeks prior to study
• Consumption of grapefruit products within 7 days prior and after study
• Dose changes of medications 14 days prior to and during study
• Active alcohol abuse or drug addiction
• Positive alcohol test at screening or after
• Excessive xanthine consumption
• Positive serology test Hepatitis B or Hepatitis C or HIV
• Excessive nicotine usage
• Positive urine screen for drugs of abuse without prescription

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (1)

NOCCR

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Kidney Diseases; Kidney Failure, Chronic

Interventions

Droxidopa

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• William D Schweiterman, MD

  Chelsea Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2011
• First Posted: November 9, 2011
• Study Start: October 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 29, 2013

Record last verified: 2013-03

Locations

US (1)