Study of Sleep-maintenance Activity of 3 Doses of SKP-1041

This study has been completed.
Sponsor:
Collaborator:
INC Research Limited
Information provided by (Responsible Party):
Somnus Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00878553
First received: March 19, 2009
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

SKP-1041 is a new formulation of a marketed sleeping agent called zaleplon. Zaleplon is currently available as Sonata as well as several generic formulations. Sonata and its generics induce sleep soon after ingestion. SKP-1041, however, is a formulation that is designed to become active 2-3 hours after ingestion. It is intended for use in people who have no trouble falling to sleep but who often awaken in the middle of the night. This trial will determine the best dose to prevent those awakenings.


Condition Intervention Phase
Sleep Disorder
Primary Insomnia
Drug: placebo
Drug: SKP-1041 (experimental formulation of zaleplon)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Double-Blind, Placebo-Controlled, Double-Dummy, Cross-Over Study to Investigate the Hypnotic Activity of Three Doses (10mg, 15mg, 20mg) of a New Zaleplon Prototype, SKP-1041, in Adults With Primary Insomnia

Resource links provided by NLM:


Further study details as provided by Somnus Therapeutics, Inc.:

Primary Outcome Measures:
  • Wake After Sleep Onset During Hours 3 to 7 Post-dose (WASO 3-7) [ Time Frame: Hours 3-7 (inclusive) after tablet ingestion ] [ Designated as safety issue: No ]
    Wake time After Sleep Onset hours 3-7 Pairwise comparisons of treatment group vs. placebo mean change from baseline in minutes per polysomnographic recording. Each patient receives baseline placebo and then each treatment dose at bedtime for two nights of sleep laboratory PSG measurements. The WASO3-7 mean of each two night visit is then used to compare placebo vs. treatment change from baseline minutes awake during hours 3 through 7 post-dose.


Secondary Outcome Measures:
  • WASO 1-8 [ Time Frame: Constantly throughout the 8 hour sleep period ] [ Designated as safety issue: No ]
    Wake Time After Sleep Onset, measured in minutes over the full 8 hour polysomnographic recording period, is summarized by treatment group for each night during the Screening and Treatment Periods.

  • Total Sleep Time 3-7 Hours Post-dose [ Time Frame: hours 3-7 (inclusive) post-dose ] [ Designated as safety issue: No ]
    Total Sleep Time during hours 3-7 (inclusive) post-dose

  • Number of Awakenings After Sleep Onset During Hours 3 to 7 Post-dose (NAASO 3-7) [ Time Frame: hours 3-7 (inclusive) post-dose ] [ Designated as safety issue: No ]
    Number of Awakenings After Sleep Onset during hours 3-7 post-dose (inclusive) as measured with PSG (polysomnography)

  • Subjective Wake Time After Sleep Onset (sWASO) [ Time Frame: 9 hours after tablet ingestion ] [ Designated as safety issue: No ]
    Subjective wake time after sleep onset sourced from the Morning Sleep Questionnaire self-assessment

  • Digit Symbol Substitution Test [ Time Frame: 9 hours after tablet ingestion ] [ Designated as safety issue: Yes ]
    Assessment of next-day residual cognitive effects. The Digit Symbol Substitution Test (DSST) explores attention and psychomotor speed. Given a code table displaying the correspondence between pairs of digits (from 1 to 9) and symbols, the patient filled in blank squares with the symbol that was paired with the digit displayed above the square. The patient was required to fill in as many squares as possible in 180 seconds.

  • Digit Span Test [ Time Frame: 9 hours post-dose ] [ Designated as safety issue: Yes ]
    Assessment of next day residual cognitive effects via testing immediate recall of numbers. The patient was given a string of digits and asked to repeat them forward, and then a second string of digits to repeat backward. The score was the number of correct responses, where the digits were repeated correctly. One point was given for each correctly repeated string of digits. The maximum subscore in the Digits Forward was 16, and the maximum subscore in the Digits Backward was 14, for a total score of 30.

  • Visual Analog Scale (Sedation) [ Time Frame: 9 hours after tablet ingestion ] [ Designated as safety issue: Yes ]
    Self-assessment of next morning sedation. Patients answered the question "How alert do you feel?" via a 100mm scale on which 0mm indicated "very sleepy" and 100mm indicated "wide awake and alert".The VAS measures a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. Operationally, a VAS is usually a horizontal line, 100 mm in length, anchored by word descriptors at each end (in this case, sleepiness and alertness). Patients were asked to mark the point on the line that they felt represented their current state. The VAS score was determined by measuring in millimeters from the left-hand end of the line to the point that the patient marked.

  • Cmax Pharmacokinetic (PK) Profile Characterization [ Time Frame: Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) ] [ Designated as safety issue: Yes ]

    A detailed characterization of the Cmax (maximum plasma concentration of SKP-1041 zaleplon in ng/mL) for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses.

    Descriptive statistics and analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis).


  • Cmax/Dose(Dose-Normalized Cmax)Pharmacokinetic (PK) Profile Characterization [ Time Frame: Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) ] [ Designated as safety issue: Yes ]

    A detailed characterization of Cmax/Dose (ng/mL/mg) (maximum plasma zaleplon concentration normalized per dose) PK profile of SKP-1041 zaleplon for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses.

    Descriptive statistics, geometric means and 90% confidence intervals were calculated for dose-normalized values of Cmax. Analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis).


  • Tmax Pharmacokinetic (PK) Profile Characterization [ Time Frame: Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) ] [ Designated as safety issue: Yes ]

    A detailed characterization of Tmax (hour) (timepoint post-dose of maximum plasma zaleplon concentration) PK profile of SKP-1041 zaleplon for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses.

    Descriptive statistics and analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis).


  • AUC Pharmacokinetic (PK) Profile Characterization [ Time Frame: Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) ] [ Designated as safety issue: Yes ]

    A detailed characterization of the AUC (area under the concentration-time curve of SKP-1041 zaleplon) for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses.

    Descriptive statistics were calculated for AUC. Analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis).


  • AUC/Dose (ng*h/mL/mg) Pharmacokinetic (PK) Profile Characterization [ Time Frame: Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) ] [ Designated as safety issue: Yes ]

    A detailed characterization of the AUC/Dose (ng*h/mL/mg) [Area under the concentration-time curve per Dose of SKP-1041 zaleplon] for each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses.

    Descriptive statistics and analysis of variance (ANOVA) for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis).


  • Half-Life (t1/2 Hour) Pharmacokinetic (PK) Profile Characterization [ Time Frame: Blood samples drawn hourly from -1 to 10 hours post-dose (except hour 7) ] [ Designated as safety issue: Yes ]

    A detailed characterization of the plasma Half-Life (t1/2 in hours) of SKP-1041 zaleplon the each of the 3 study doses within the Pharmacokinetic Population (patients who completed the PK substudy--night 3 of Visit 6)with subsequent descriptive statistics comparing key PK characteristics across the 3 doses.

    Descriptive statistics and analysis of variance (ANOVA)for independent groups compared the three dosage groups using the untransformed values, as well as following rank transformation(nonparametric analysis).



Enrollment: 67
Study Start Date: May 2010
Study Completion Date: August 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Two placebo tablets administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence
Drug: placebo
tablet at bedtime
Other Name: sugar pill
Experimental: 10 mg SKP-1041
One 10 mg SKP-1041 controlled release zaleplon tablet plus one placebo tablet administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence
Drug: SKP-1041 (experimental formulation of zaleplon)
tablet at bedtime
Other Name: zaleplon
Experimental: 15 mg SKP-1041
One 15 mg SKP-1041 controlled release zaleplon tablet plus one placebo tablet administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence
Drug: SKP-1041 (experimental formulation of zaleplon)
tablet at bedtime
Other Name: zaleplon
Experimental: 20 mg SKP-1041
Two 10 mg SKP-1041 controlled release zaleplon tablets administered orally at bedtime for two consecutive nights to each patient per crossover randomized sequence
Drug: SKP-1041 (experimental formulation of zaleplon)
tablet at bedtime
Other Name: zaleplon

Detailed Description:

Patients will participate in the study for approximately 44 to 56 days, including a 14- to 21-day Screening Period, 4 Treatment Periods each followed by washout periods, and a final Follow-up Visit. Patients will receive their randomly assigned study medication and spend 2 nights in a sleep laboratory, subsequently returning home for a 4- to 7-day washout period between each treatment period. The fourth and final treatment period will include a third night at the site during which all patients will continue to receive the same study medication as on the first 2 nights of this treatment period. Blood will be drawn from all patients for pharmacokinetic analyses at specific time intervals. Patients will undergo final safety assessments 2 to 5 days after the last dose of study medication.

  Eligibility

Ages Eligible for Study:   21 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary insomnia characterized by chronic difficulty maintaining sleep

Exclusion Criteria:

  • History of restless legs syndrome, sleep apnea, narcolepsy, or parasomnias;
  • Any clinically relevant acute or chronic diseases which could interfere with the patient's safety during this trial or with this tablet's absorption;
  • Pregnancy;
  • History of medication allergies;
  • Use of medication that might interfere with this study;
  • Recent travel across more than 3 time zones.
  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: NCT00878553

Sponsors and Collaborators
Somnus Therapeutics, Inc.
INC Research Limited
Investigators
Principal Investigator: Jon Freeman, PhD Clinilabs, Inc.
Principal Investigator: Steven G. Hull, MD Vince and Associates Clinical Research
Principal Investigator: Russell Rosenberg, PhD Neurotrials Inc.
Principal Investigator: James K. Walsh, PhD Sleep Medicine and Research Center
Principal Investigator: David J. Seiden, MD Broward Research Group
Principal Investigator: Helene A. Emsellem, MD Emsellem MD PC
Principal Investigator: D. Alan Lankford, PhD Sleep Disorders Center of Georgia
Principal Investigator: Beth E. Safirstein, MD MD Clinical
  More Information

No publications provided

Responsible Party: Somnus Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00878553     History of Changes
Other Study ID Numbers: SOM201
Study First Received: March 19, 2009
Results First Received: January 7, 2013
Last Updated: January 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Somnus Therapeutics, Inc.:
insomnia
middle of the night
sleep maintenance

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Sleep Disorders
Parasomnias
Sleep Disorders, Intrinsic
Dyssomnias
Nervous System Diseases
Mental Disorders
Neurologic Manifestations
Signs and Symptoms
Zaleplon
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants

ClinicalTrials.gov processed this record on July 24, 2014