Primary objective1. To determine the effect of food on the pharmacokinetics of buspirone administered as the Lybridos formulationSecondary objective1. To evaluate the safety and tolerability of a single dose of Lybridos under fasted and fed…
ID
Source
Brief title
Condition
- Sexual dysfunctions, disturbances and gender identity disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic
90% CI ratio for both AUC0-inf and Cmax
Secondary outcome
Pharmacokinetic
Difference in Tmax and tlag
and
- Area under the concentration time curve (AUC)
- Peak exposure (Cmax)
- Time to peak exposure (Tmax)
- Lag time (tlag)
- Terminal elimination half-life (t*)
Safety
A. Nature, frequency and severity of AEs
B. Vital signs and 12-lead ECG
C. Safety laboratory tests (urinalysis, haematology, biochemistry)
Background summary
Sexual dysfunction
In many mammalian species, female sex steroids are necessary for the expression
of female sexual behaviour. In most animals, copulation is limited to the
period of ovulation. Humans (as well as higher primates), however, show sexual
intercourse also outside the periovulatory period. Testosterone is involved in
female sexual behaviour. A complete loss, decreased libido, or absence of
desire for sexual activity is common after bilateral oophorectomy,
adrenalectomy, and after natural menopause, while substitution with
testosterone has been shown to improve sexual motivation and performance.
The 3 (transitional and overlapping) phases of the human sexual response can
each be disrupted, leading to low sexual desire, sexual arousal problems, and
hampered orgasm. The phases are regulated by relatively independent
neurotransmitter functions, and dysfunctions may be amenable to
psychopharmacological treatment. Traditionally, motivated behaviours have been
divided into appetitive and consummatory components. Activities aimed at
obtaining reward and satisfactions belong to the appetitive component. The
fundamental appetitive motivational process is an intrinsic brain function and
is especially related to the predictive value of stimuli for reward.
Processing of motivationally relevant information (i.e., stimuli predicting
reward) causes an increase in activity of the meso-accumbens dopaminergic
system (i.e., dopamine neurons of the ventral tegmental area [VTA] innervating
the nucleus accumbens). The activity of this system is increased during
flexible approach behaviour when anticipating reward related to copulation.
Increasing activity in these dopaminergic pathways facilitates sexual
motivation, in particular anticipatory sexual behaviour.
Anticipating sexual reward will produce arousal of the genitals, in which at
least 2 key neurotransmitters are involved: acetylcholine and nitric oxide
(NO). Acetylcholine and NO both promote erections in men and lubrication and
swelling in women. Orgasm, the consummatory phase of human sexual response, is
facilitated by descending spinal noradrenergic fibres and innervation of the
genitals, and inhibited by descending spinal serotonergic fibres.
Study objective
Primary objective
1. To determine the effect of food on the pharmacokinetics of buspirone
administered as the Lybridos formulation
Secondary objective
1. To evaluate the safety and tolerability of a single dose of Lybridos under
fasted and fed conditions
Study design
This will be a randomized, open-label balanced two-period, two-treatment,
two-sequence crossover study in healthy female subjects to evaluate the effect
of food on the pharmacokinetics (PK) of buspirone after a single dose of
Lybridos. In addition, safety and tolerability of Lybridos administered after
fed and fasted conditions will be evaluated.
All subjects will complete a screening visit. Prior to the day of dosing,
eligible subjects will stay overnight (O/N) (at least 10 hours) in an
environment controlled for fasting conditions. An intravenous cannula will be
placed in a vein in each subject prior to dosing (if possible) to provide
access for regular blood sampling.
Randomization will ensure that each subject will receive each of the following
treatments (A and B) on two separate occasions, being:
A. Fed + Lybridos
B. Fasted + Lybridos
And is assigned to one of the following treatment sequences: A-B or B-A.
On the day of dosing, subjects in treatment A will take a high fat, high
calorie meal (50% of the caloric intake of 800-1000 kcal) on site. Lybridos is
administered 30 minutes after the start of the food intake and the meal should
be completed within this 30 minutes time frame. No intake of water is allowed
the hour prior to and 1 hour post administration of the drug. Lybridos will be
taken with 240 mL water and subject will abstain from food intake the following
4 hours. The food intake will be standardized for all patients during 12 hours
post dose.
For subjects in treatment B, administration of Lybridos is taken with 240 mL
water. No intake of water is allowed the hour prior to and 1 hour post
administration of the drug. Next 4 hours, the subject will abstain from food
intake. The food intake will be standardized for all patients during 12 hours
post dose.
Both periods will be separated by a washout period of at least 1 week between
the dosing of the 1st period and dosing of the 2nd period.
Intervention
NA
Study burden and risks
NA
Louis Armstrongweg 78
Almere 1311 RL
NL
Louis Armstrongweg 78
Almere 1311 RL
NL
Listed location countries
Age
Inclusion criteria
1. Provision of written informed consent
2. Females between 18 and 55 years of age (both inclusive)
3. Healthy based on medical history, physical examination, electrocardiogram, laboratory values and vital signs
4. Body mass index (BMI) >=18 kg/m2 and <= 30 kg/m2
5. Venous access sufficient to allow blood sampling as per protocol;
Exclusion criteria
1. Systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg
2. Systolic blood pressure < 90 mmHg and/or diastolic blood pressure< 50 mmHg
3. Use of oral contraceptive containing anti-androgens (e.g. cyproteron) or anti(androgenic) progestogens (drospirone, dienogest, chlormadinone acetate and norgestrel)
4. Use of any or hormone replacement therapy (HRT) containing more than 50 µg/day of estrogen
5. Pregnancy (note: an urine pregnancy test will be performed in all women prior to the administration of study medication)
6. Lactating or delivery in the previous 6 months
7. Perimenopausal status (cycle shortening/irregular menstrual bleeding in the last 12 consecutive months and/or occurrence of vasomotor symptoms (e.g. hot flashes, night contraceptive sweating) in combination with elevated FSH levels (>40 IU/L) for women from age 40 onwards; in women with a history of hysterectomy, perimenopausality can be assessed by FSH levels (> 40 IU/L) and/or vasomotor symptoms)
8. Use of any drugs from two weeks prior to admission to the research unit until the follow-up visit, except for allowed oral contraceptives and pain relief (e.g. paracetamol up to 1.5 g per day)
9. Known or suspected hypersensitivity to any of the components of the formulation
10. Liver function tests (i.e., ALT, AST and bilirubin) significantly above the upper limit of normal at repeated measures
11. Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic as judged by the medical investigator
12. Smoking
13. Unwilling or unable to refrain from consuming grapefruit juice, star fruit, and St. Johns Wort 24 hours before and after intake of medication
14. Current regular use of any illicit drugs or history of excessive drinking within 3 months prior to admission to the research unit and/or unwilling or unable to refrain from products containing alcohol from 24 hours before admission and during the stay in the research unit
15. Donation of blood within 3 months prior to admission to the research unit
16. Positive serology test for HBsAg, anti HAV (IgM), anti HCV or anti HIV 1+2
17. Subjects who, in the opinion of the investigator, are not likely to complete the trial for any reason
18. Participation in any clinical study within 1 month prior to the expected date of enrolment into the study.
19. Employees of the sponsor or CRO involved in the study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003318-99-NL |
| CCMO | NL50357.056.14 |
| OMON | NL-OMON22366 |