PK Study of Intranasal RX0041-002 in Subjects With Severe Renal Impairment and Normal Renal Function

• Status: Completed
• Trial end date: 2016-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate the potential effect of renal impairment on the systemic pharmacokinetics of acute Intranasal RX0041-002. The secondary objective is to evaluate the safety and tolerability of acute Intranasal RX0041-002 in subjects with normal renal function and severe renal impairment.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Pharmaceutical Project Solutions, Inc.
• Collaborator: Cognitive Research Corporation

Criteria

Inclusion Criteria:

1. Male or female.

2. Greater than or equal to 18 years of age and able to understand and comply with protocol requirements, provide written informed consent and HIPPA authorization; ± 10 years for individual age-matched controls.

3. Females (if of child-bearing potential and sexually active) and males (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method from the first dose and for 8 days following administration of study drug. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include abstinence, birth control pills or patches, diaphragm, intrauterine device (IUD), condom, surgical sterilization, and progestin implant or injection. Prohibited methods include: the rhythm method or withdrawal.

4. BMI ≥ 18 ≤ 42 (see Appendix); ± 20% for BMI-matched controls

5. In general, good health aside from renal disease and associated conditions as ascertained by physical examination (PE) including measurement of supine and standing vital signs, medical history, clinical laboratory studies, and 12-lead electrocardiogram (ECG).

6. For assignment to the normal renal function (control) group, subjects must have an eGFR ≥ 90 mL/min/1.73m2 at screening. Assignment to the severe renal impairment group will be based upon an eGFR of 15-29 mL/min/1.73m2 at screening.

7. Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance.

Exclusion Criteria:

1. Has a known allergy to any ester based anesthetics including cocaine HCl, procaine, tetracaine, chloroprocaine, dibucaine, or benzocaine amide based anesthetic allergies are NOT exclusionary. Amide based anesthetics are : lidocaine, mepivicaine, bupivicaine, levobupivicaine, ropivicaine, etidocaine, prilocaine, and articaine.

2. Concurrent use of medications known to affect the elimination of serum creatinine (eg, trimethoprim/sulfamethoxazole [Bactrim®] or cimetidine [Tagamet®]) and competitors of renal tubular secretion (eg, probenecid) within 30 days prior to the first dose of study drug.

3. Presence of significant gastrointestinal, liver or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects.

4. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study.

5. The use of amphetamines, methylphenidate or other stimulant prescription and nonprescription products such as pseudoephedrine, bronchial inhalers containing sympathomimetics (epinephrine or other beta-receptor agonist) or herbal products in the 7 days prior to screening or has a need to use these drugs during the course of the study.

6. Use of any selective serotonin and norepinephrine reuptake inhibitorsserotonin-specific reuptake inhibitors antidepressants or tricyclic antidepressant up to7 days or 5 half-lives (whichever is longer) prior to screening or has a need to use these drugs during the screening period and throughout the time period of the trial.

7. Use of Monoamine oxiadse inhibitors drugs up to 14 days prior to screening or has a need to use these drugs during the screening period and throughout the time period of the trial.

8. History of hepatitis

9. Elevated aspartate aminotransferase/alanine aminotransferase/bilirubin,

10. HIV

11. Excessive use of alcohol/tobacco/caffeine

12. Less than 18 years of age.

13. Has previously received study drug.

14. Has a history of abuse of controlled substances, nasal or otherwise, or has damage to the nasal space, that in the opinion of the investigator might interfere with the ability to absorb RX0041-002.

15. Has severely traumatized mucosa or sepsis in the nasal cavity.

16. Has participated in an investigational study or received an investigational drug within 30 days preceding the randomization.

17. Is a pregnant or nursing mother.

18. Has a positive pregnancy test at Screening or Day -1.

19. Has a history of seizure, with the exception of febrile seizures.

20. Has symptomatic cardiovascular disease, moderate to severe hypertension.

21. Has a known personal or family history of hereditary pseudocholinesterase deficiency. Study participants will be screened by asking about personal or family history of anesthetic reaction, anesthetic death, and previous diagnosis of psuedocholinesterase deficiency in a relative or personally. Subjects identified with pseudocholinesterase deficiency are at risk for delayed recovery with certain anesthetics (e.g. succinylcholine and ester-based anesthetics).

22. Has a known personal or family history of pheochromocytoma. Study participants will be specifically asked if they have been treated for a pheochromocytoma previously or if they have a family member who has been diagnosed with pheochromocytoma (since 10% of these are familial).

23. Has a known personal or family history of adrenal tumor.

24. Clinically significant ECG abnormalities, based upon the impression of the investigator.

25. Has a positive urine test result for drugs of abuse (amphetamines, barbiturates, cocaine metabolites, opiates and oxycodone) or cannabinoids at Screening or on Day 1.

26. Blood chemistry values judged clinically significant by the investigator. aa. Donation of blood (one pint or greater) within four weeks prior to administration of study medication.

bb.Use or intended use of any drug or other product that inhibits or induces cytochrome P450 (CYP) 3A4 within 14 days prior to or during the conduct of the study.

cc.Taking drugs or natural herbal supplements (including St. John'sWort) with known interactions with CYP or with the study drug.

dd.Has consumed or is unwilling to refrain from consumption of foods containing grapefruit, pomelo or Seville oranges from within 7 days prior to Day 1 until end of study.

ee.Not suitable for entry into the study in the opinion of the investigator.

Note: A one-time retest is permitted for any blood test if the original sample was hemolyzed.