Safety, Tolerability, Pharmacodynamic and Pharmacokinetics of a Single Rectal Application of 10 mg NRL001 in Elderly Subjects

NCT01099683 | Completed Phase 1

• 2 other identifiers: NRL001-02/2009 (SAGE)2009-017475-16
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

A total of 26 healthy elderly male and female subjects will receive both 10 mg NRL001 in a 2 g rectal suppository and placebo in this double-blind, cross-over study. The order of treatment will be randomised, with a minimum washout period of 3 days between doses. An end of study assessment will be conducted at least 7 days after administration of the last treatment. The pharmacokinetics of NRL001 will be determined prior to, and after, dosing. Pharmacodynamics will be examined using a three lead Holter monitor during both treatment periods. Adverse Events, vital signs, ECGs and clinical laboratory parameters will be collected, tabulated, reviewed and recorded throughout the study.

Conditions

Fecal Incontinence

Outcome Measures

Primary Outcomes (1)

• Pharmacodynamic effects of NRL001

  4 hours post-administration

Secondary Outcomes (2)

• Pharmacokinetics of NRL001

  30 hours post-administration

• Safety will be assessed by recording adverse events (AEs), vital signs, 12-lead ECG, physical examinations and clinical laboratory tests.

  Throughout the study period

Study Arms (2)

NRL001

EXPERIMENTAL

All subjects will receive 10 mg NRL001 in a 2 g rectal suppository

Drug: NRL001

Placebo

PLACEBO COMPARATOR

All subjects will receive placebo

Drug: Placebo

Interventions

NRL001 DRUG

Single rectal administration of 2 mg NRL001 in a 2 g suppository

NRL001

Placebo DRUG

All subjects will receive rectal suppository containing placebo

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Volunteers will be included in the study if they satisfy the following criteria:
• Healthy adult male or female volunteers (as determined by medical history, physical examination, laboratory test values, vital signs and electrocardiograms \[ECGs\] at screening) aged ≥65 years.
• Non-smokers from 3 months before receiving the first dose and for the duration of the study.
• Body mass index (BMI) ≥ 18 and ≤ 32 kg/m2.
• Able and willing to receive rectal treatments.
• Able to voluntarily provide written informed consent to participate in the study.
• Sexually active male volunteers must use condoms with their partners throughout the study and for 90 days after completion of the study in addition to their partner's normal mode of contraception.
• Male volunteers must not donate sperm during the study and for 90 days after completion of the study.
• Must understand the purposes and risks of the study and agree to follow the restrictions and schedule of procedures as defined in the protocol.
• Female volunteers must be postmenopausal (for at least 1 year, confirmed by FSH testing at screening).
• Must be willing to consent to have data entered into The Over Volunteering Prevention System (TOPS).
• The volunteer's primary care physician must confirm that there is nothing in their medical history that would preclude their enrolment into this clinical study.

You may not qualify if:

• Volunteers will be excluded if they fulfil any of the following criteria:
• Positive for HIV, hepatitis B, or hepatitis C as demonstrated by the results of testing at screening.
• History or presence of any significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal (GI), endocrine or immunologic disease.
• History or presence of any clinically significant ano-rectal conditions as judged by the Investigator (e.g. concomitant enlarged symptomatic haemorrhoids or acute presence of anal fissures) or clinically significant drug allergy.
• Blood pressure in excess of 150/90 mmHg or pulse rate below 50 beats per minute at screening.
• Any significant illness during the screening period preceding entry into this study.
• Clinically relevant ECG-abnormalities (e.g. QTc prolongation, acute arrhythmia) during the screening assessment
• Laboratory values which are abnormal and deemed to be clinically significant according to Bio-Kinetic Europe Ltd. SOPs, unless agreed in advance by the Sponsor's Responsible Medical Officer and the Bio-Kinetic Investigator.
• Current or history of drug or alcohol abuse or a positive drugs of abuse test at screening or check in.
• Use of any disallowed concomitant medication, including over-the-counter items within 14 days prior to study drug administration until the end of the study.
• Use of any medication applied via the rectum, within 30 days prior to dosing
• Use of any medication currently or within 30 days prior to dosing which the Investigator believes may affect the study participation or results.
• Participation in a clinical drug study during the 90 days preceding the initial dose in this study.
• Donation of blood or blood products within 90 days prior to study drug administration, or at anytime during the study, except as required by this protocol.
• History of any allergy to medication, particularly nifedipine, α adrenoceptor antagonists or latex

Sponsors & Collaborators

• Norgine: lead

Study Sites (1)

Bio-Kinetic Europe Ltd

Belfast, BT2 7BA, United Kingdom

Location

Related Publications (1)

• Bell D, Duffin A, Gruss HJ, Pediconi C, Jacobs A. A randomised, controlled, crossover study to investigate the pharmacodynamics, pharmacokinetics and safety of 1R,2S-methoxamine hydrochloride (NRL001) in healthy elderly subjects. Colorectal Dis. 2014 Mar;16 Suppl 1:27-35. doi: 10.1111/codi.12543.

  PMID: 24499494 DERIVED

MeSH Terms

Conditions

Fecal Incontinence

Condition Hierarchy (Ancestors)

Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• David Bell, MRCGP MFPM

  Bio-Kinetic Europe, Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 15, 2010
• First Posted: April 7, 2010
• Study Start: April 1, 2010
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: December 24, 2010

Record last verified: 2010-12

Locations

GB (1)