Safety and Pharmacokinetics of Multiple Rising Oral Doses of BI 224436 in Healthy Male Volunteers.

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01276990
First received: January 13, 2011
Last updated: February 8, 2012
Last verified: February 2012
  Purpose

To investigate the safety and pharmacokinetic of BI 224436 in healthy male volunteers following oral administration of repeated doses for 10 days within 8 dosing regimens.


Condition Intervention Phase
HIV Infections
Healthy
Drug: BI 224436
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Safety and Pharmacokinetics of Multiple Rising Oral Doses of BI 224436 ZW (Powder in Bottle Formulation) at 12.5 mg q24h, 12.5 mg q12h, 12.5 mg q8h, 25 mg q12h, 25 mg q8h, 50 mg q12h, 37.5 mg q8h and 50 mg q8h Dose Levels for 10 Days in Healthy Male Volunteers (Randomized, Double-blind Placebo-controlled Within Dose Groups)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Changes in blood pressure [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Changes in pulse rate [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Changes in 12-lead ECG [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Changes in clinical laboratory test parameters [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cmax,ss (maximum measured concentration of the analyte in plasma at steady-state over a uniform dosing interval t) [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady-state) [ Time Frame: 10 Days ] [ Designated as safety issue: No ]
  • Cmin,ss (minimum concentration of the analyte in plasma at steady-state over a uniform dosing interval t) [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady-state over a uniform dosing interval t) [ Time Frame: 13 days ] [ Designated as safety issue: No ]
  • t1/2,ss (terminal half-life of the analyte in plasma at steady-state) [ Time Frame: 13 days ] [ Designated as safety issue: No ]
  • CL/F,ss (apparent clearance of the analyte in the plasma at steady-state following extravascular multiple dose administration) [ Time Frame: 13 days ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: January 2011
Estimated Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Matching placebo in dosing regimen 1-8
Drug: BI 224436
Oral drinking solution
Drug: Placebo
Oral drinking solution
Experimental: BI 224436 dosing regimen 1
Dosing regimen 1
Drug: BI 224436
Oral drinking solution
Experimental: BI 224436 dosing regimen 2
Dosing regimen 2
Drug: BI 224436
Oral drinking solution
Experimental: BI 224436 dosing regimen 3
Dosing regimen 3
Drug: BI 224436
Oral drinking solution
Experimental: BI 224436 dosing regimen 4
Dosing regimen 4
Drug: BI 224436
Oral drinking solution
Experimental: BI 224436 dosing regimen 5
Dosing regimen 5
Drug: BI 224436
Oral drinking solution
Experimental: BI 224436 dosing regimen 6
Dosing regimen 6
Drug: BI 224436
Oral drinking solution
Experimental: BI 224436 dosing regimen 7
Dosing regimen 7
Drug: BI 224436
Oral drinking solution
Experimental: BI 224436 dosing regimen 8
Dosing regimen 8
Drug: BI 224436
Oral drinking solution

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  1. Healthy male according to the following criteria: based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), clinical laboratory tests.
  2. Age >=18 and <=50 years.
  3. Body Mass Index (BMI) >=18.5 and BMI <=32 kg/m2.
  4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation.
  5. Documented to be sterile; or, if can father a child, agree to abstain from sexual intercourse during and at least seven days following last study drug administration, or are willing to use condoms during the same period each time (Subject's female sexual partner(s) of child-bearing potential should be willing to use either ethinyl estradiol containing oral contraceptives or a reliable barrier method of contraception).

Exclusion criteria:

  1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance according to the opinion of the investigator.
  2. Any evidence of a clinically relevant concomitant disease.
  3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders.
  4. Surgery of the gastrointestinal tract that in the opinion of the investigator may affect the absorption.
  5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders.
  6. History of relevant orthostatic hypotension, fainting spells or blackouts.
  7. History or evidence of Human Immunodeficiency Virus or other chronic or relevant acute infections, including Hepatitis C Virus and Hepatitis B Virus infection.
  8. History of relevant allergy / hypersensitivity (including allergy to investigational medicinal product or its solvent).
  9. History of any familial skeletal muscle disorder, or history of Creatine Kinase (CK) elevation not due to strenuous physical activity or trauma.
  10. Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial.
  11. Use of drugs, including prescription and non-prescription drugs, and St. Johns Wort which might reasonably influence the results of the trial within 14 days prior to study drug administration or during the trial, or consumption of grapefruit, grapefruit juice, orange juice, Seville oranges, green tea, pineapple, pineapple juice, broccoli or red wine within 3 days prior study drug administration or during the trial.
  12. Participation in another trial with an investigational drug within one month prior to administration or during the trial.
  13. Current smoker (>10 cigarettes or >3 cigars or >3 pipes / day).
  14. Inability to refrain from smoking during the trial.
  15. Alcohol abuse (more than 30 g day).
  16. Drug abuse.
  17. Blood donation (more than 100 mL within four weeks prior to administration or during the trial).
  18. Physical activity in excess of usual activity of daily living (e.g., fitness physical exercise, physical labor) within 7 days prior to study drug administration until end of study visit.
  19. Any laboratory value outside the reference range that in the opinion of the investigator is of clinical relevance.
  20. A marked baseline prolongation of QT or corrected QT (QTc) intervals (e.g., repeated demonstration of a QTc interval >450 ms); or, other ECG abnormality of clinical significance.
  21. A history of additional risk factors for Torsades de points (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
  22. CK at screening =2x Upper Limit of Normal (ULN) (If CK is =2xULN and <5xULN one retest will be allowed to verify the result).
  23. CK at baseline (Day -1) >ULN (If CK is >ULN and <1.5xULN one retest will be allowed to verify the result).
  24. Thyroid - stimulating hormone outside normal reference range, or history of hypo-or hyperthyroidism.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01276990

Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01276990     History of Changes
Other Study ID Numbers: 1277.2
Study First Received: January 13, 2011
Last Updated: February 8, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on October 02, 2014