WO2024180475A1 - Lipid composition for the combined treatment of cystic fibrosis - Google Patents

Abstract

The invention relates to a lipid composition for oral administration comprising a combination of medium-chain fatty acids and long-chain polyunsaturated fatty acids for use in the simultaneous, separate or sequential treatment of cystic fibrosis in a population of individuals at least 2 years of age, having at least one F508 (F508del) mutation in the transmembrane conductance regulator gene and undergoing treatment with CFTR protein modulating drugs.

Description

LIPID COMPOSITION FOR THE COMBINED TREATMENT OF

CYSTIC FIBROSIS

FIELD OF THE INVENTION

The present invention relates to a lipid composition for the combined treatment of cystic fibrosis.

In one aspect, the present invention relates to an oral lipid composition to be administered in combination with CFTR protein modulating and/or correcting drugs, in a therapeutic scheme comprising the administration of at least one of Ivacaftor, Tezacaftor, Elexacaftor to increase their absorption in the gastrointestinal tract and increase their bioavailability and therapeutic activity.

The lipid composition is suitable for administration in a population of individuals who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Typically, this patient population is affected by cystic fibrosis and in most cases has a chronic diffuse inflammatory state.

BACKGROUND

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by a mutation in the CFTR gene, which codes for a protein that acts as a chloride channel and is known as CFTR (Cystic Fibrosis Transmembrane conductance Regulator). In cystic fibrosis (CF), there is a deficiency and/or malfunction of the CFTR gene, which encodes a protein used at the cellular level to transport water and chlorine, which, when dysfunction occurs, can cause, among other disorders, the formation of thick mucus in the lungs and pancreas in the affected individual.

Cystic fibrosis is the most common fatal hereditary genetic disease in the Caucasian population, since it affects about 1 in every 2,500 individuals. Symptoms involve different internal organs and are attributable to the abnormality in chloride excretion, normally mediated by the protein encoded by the CFTR gene. This alteration leads to the secretion of mucus that is very thick and viscous and therefore flows poorly. The consequent obstruction of the main ducts causes the main symptoms (occurrence of recurrent lung infections, pancreatic insufficiency, steatorrhea, liver cirrhosis, intestinal obstruction, and male infertility), with a diffuse chronic inflammatory state.

Although more than 1,500 mutations have been identified, deletion of the amino acid phenylalanine at position 508 (F508del) is the most frequently observed. In children, CF is the leading cause of severe chronic lung disease and is responsible for most exocrine pancreatic insufficiencies.

Over the past four decades, significant improvement in the survival of individuals with CF has been observed due to specialized patient management, improved techniques for maintaining airway patency, availability of appropriate antibiotics, early diagnosis of mandatory expanded newborn screening, and improved management of nutritional problems.

In particular, a key role in patient management has been played by nutrition, since approximately 50% of individuals have malnutrition due to an imbalance between calories intake and energy expenditure, caused partly by malabsorption and partly by increased energy consumption.

To date, international guidelines on the nutrition of children and adults with cystic fibrosis have provided adequate indications on nutritional management, suggesting calorie supplementation to counteract malabsorption so as to improve outcomes in terms of growth and nutritional balance.

Nutritional indications, although difficult to standardize given the need for customization that is dependent on individual growth parameters, consider hypercaloric and hyperlipid diets generally suitable for all individuals with the disease.

Among lipids, of particular importance are omega-3 s, in particular DHA, the administration of which is suggested by the reference guidelines on food supplementation in patients with cystic fibrosis with dosages of at least 1 g/day in adults and 100 mg/kg/day in the first year of life.

Alongside the nutritional indications and dietary regimens to be adopted in the management of patients with cystic fibrosis, increasingly effective pharmacological therapies have been developed.

Among them, pharmacological therapies based on CFTR protein modulators, especially Kaftrio® or Trikafta®, from Vertex Pharmaceuticals Inc., are considerably changing the nutritional management of cystic fibrosis patients.

Kaftrio® is a drug/therapeutic treatment based on a combination of the active ingredients Ivacaftor (enhancer of CFTR channel protein function), Tezacaftor and Elexacaftor (correctors of defective CFTR protein function), indicated, typically in combination with Ivacaftor, in the treatment of cystic fibrosis in patients aged 2 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

The new modulator is the drug with the best outcomes among those available so far, both in terms of the percentage of patients for whom it is indicated (about 70% of Italian patients, more than 80% of American patients) and in terms of the results demonstrated so far.

In particular, this therapeutic treatment results in increased pulmonary function FEV1, reduced pulmonary infectious flare-ups and hospitalizations, more than 1 point improvement in nutritional status as measured by body mass index, lowered sweat test value - indicative of significant improvement in chloride channel function, significant improvement in quality of life as measured by the standardized CFQ-R questionnaire.

Kaftrio®, combined with Ivacaftor, is on the market in tablet or granule sachet form, and their administration is recommended in the morning and evening, at regular 12-hour intervals according to the dosage recommendation of the drug Vertex.

Taking the drug is recommended in conjunction with meals that are rich in lipids of any type and origin, for example meals or snacks containing butter or oil, or those containing eggs, cheese, nuts, whole milk, or meat. In fact, the absorption and therapeutic efficacy of the active ingredients of the therapeutic scheme is increased by taking a moderate-fat meal with respect to administration when fasting. Absorption pharmacokinetics studies carried out by the drug manufacturer indicate for Elexacaftor (ELX) and Ivacaftor (IVA) an increase in exposure of about 1.9-2.5 times and 2.5-4 times, respectively, if the tablet or granules are taken with a moderate-fat meal, while food appears to have no effect on the absorption of Tezacaftor (TEZ). The latest clinical data and related international recommendations, aimed at ensuring proper absorption of each dose of the drug, are geared toward quantities of 10-20 g of lipids in the case of adolescent and adult patients, to be reduced to 5-10 g per single administration in the case of pediatric patients. Although general nutritional guidance is currently available regarding the proper introduction of foods containing saturated, monounsaturated and/or polyunsaturated fats into the dietary regimen of individuals with cystic fibrosis and treated with CFTR modulating drugs, at present there is no nutritional product and administration regimen suitable to facilitate intake and improve the absorption of CFTR modulators, in particular the drug Kaftrio®.

Therefore, the aim of the invention is to provide a composition for oral administration containing a combination of selected lipids to improve gastrointestinal absorption of CTFR protein modulators, specifically selected from Ivacaftor, Tezacaftor and Elexacaftor, or a combination thereof, for example in the drug Kaftrio®.

An object of the invention is to provide a composition based on lipids selected to increase the absorption in the gastrointestinal tract of CTFR protein modulating drugs, in particular the drug Kaftrio®, and thereby increase their bioavailability in the human body and their therapeutic efficacy in the treatment of cystic fibrosis.

SUMMARY OF THE INVENTION

The inventors have surprisingly found that in a population of individuals with cystic fibrosis with at least one F508 mutation in the transmembrane conductance regulator gene undergoing treatment with CFTR protein modulators, therapeutic response is improved by supplementing the dietary regimen with a lipid composition comprising specific medium-chain fatty acids (MCT/Medium-Chain Triglycerides) and polyunsaturated fatty acids, preferably long-chain fatty acids (LCPUFA).

This improvement can be attributed to an improvement in the absorption and/or metabolism of the administered CFTR protein modulators, achieved by simultaneous, separate, or sequential administration of the lipid composition described herein, for example, before or within an hour of administration of the triple drug Ivacaftor, Tezacaftor, and Elexacaftor, and/or of Ivacaftor alone.

Advantageously, the lipid composition according to the invention comprises a combination of medium-chain fatty acids and long-chain polyunsaturated fatty acids which allows to increase the absorption and efficacy of a CFTR protein modulator preferably selected from Ivacaftor, Tezacaftor, Elexacaftor, and mixtures thereof, preferably in a combination regimen with Ivacaftor.

Preferably, the lipid composition described herein is formulated with amounts of medium-chain fatty acids and long-chain fatty acids, in particular docosahexaenoic acid, adapted to provide a source of energy for the body and to counteract the inflammatory state of cystic fibrosis patients.

According to a first aspect, the invention relates to a lipid composition for oral administration comprising a combination of mediumchain fatty acids and long-chain fatty acids for use in the simultaneous, separate, or sequential treatment of cystic fibrosis in a population of individuals of age 2 or more, with at least one F508 mutation (F508del) in the transmembrane conductance regulator gene and undergoing treatment with CFTR protein modulators.

The benefits obtained with the treatment of the composition for the uses according to the invention can be found in a reduction of inflammatory processes, in particular of the lungs, resulting in an increase in lung function and/or reduction in flare-ups of lung infections, an improvement in cellular chloride channel function and in quality of life as measured by the standardized CFQ-R questionnaire.

The invention also relates to a lipid composition comprising a combination of medium-chain fatty acids and long-chain polyunsaturated fatty acids for use in increasing enteric uptake of a CTFR protein modulator in a population of individuals 2 years of age or older with at least one F508 (F508del) mutation of the transmembrane conductance regulator gene.

Preferably, the lipid composition described herein is administered, either separately, sequentially, or simultaneously with CFTR protein modulators selected from Ivacaftor, Tezacaftor, Elexacaftor, and mixtures thereof, preferably in a treatment regimen comprising, preferably within 24 hours, more preferably 12 hours +/- 1 hour apart, a subsequent administration of Ivacaftor.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with one aspect, the Applicant, starting from the observation that administration of a lipid composition based on mediumchain fatty acids and long-chain polyunsaturated fatty acids increases the absorption of CFTR modulators, as described herein further unexpectedly found that this lipid composition increases the therapeutic efficacy of CFTR modulators, specifically the drug Kaftrio®, in a population of subjects aged 2 years and older with at least one F508 (F508del) mutation of the transmembrane conductance regulator gene. In particular, an unexpectedly marked reduction in the inflammatory component present in individuals with cystic fibrosis was observed.

Therefore, the present invention relates to an oral lipid composition for combined use according to claim 1.

Within the scope of the invention, suitable fatty acids comprise medium-chain triglycerides, known by the acronym MCT (Medium Chain Triglycerides), which preferably comprise or consist of fatty acids with chains of 6 to 12 carbon atoms, for example, C:6 caproic acid, C:8 caprylic acid, C: 10 capric acid, and C: 12 lauric acid, more preferably with 8 and/or 10 carbon atoms, C:8-C: 10.

Advantageously, these medium-chain triglycerides, with the exception of lauric acid, are easily absorbed in the intestine and are transferred directly into portal circulation without first passing through the lymphatic route. Preferably, lauric acid is minimally contained in the composition described herein, preferably it may be contained in an amount smaller than or equal to 8% by weight preferably for approximately 5-8% in the mixture in which for example the C:8+C:10 MCTs constitute at least 85% by weight. In certain embodiments lauric acid is absent in the composition.

The triglycerides that contain them have better water solubility than their long-chain counterparts and are therefore more easily attacked by gastrointestinal lipases and therefore do not require the action of bile salts to be digested.

MCTs then freely enter the mitochondria at the hepatic level, where B-oxidation is completed with production of readily available energy in the form of ketone bodies, which are also useful in reducing inflammatory processes in the human body. Suitable MCTs used as an energy source for the human body are caprylic acid (C:8) and capric acid (C: 10) or mixtures thereof.

The long-chain polyunsaturated fatty acids (LCPUFAs) used in the invention are fatty acids that have more than one C=C double bond within the molecule. Polyunsaturated fatty acids can assume a cis or trans form depending on the conformational geometry of the molecule. The double bonds are typically isolated, with a methylene bridge (-CH2-) between 2 double bonds, or conjugated, with a single bond between 2 double bonds.

Suitable polyunsaturated fatty acids comprise omega-3 s and omega- 6s, which are considered essential because they cannot be synthesized by the body and therefore must necessarily be taken in with the diet.

The lipid composition according to the invention contains polyunsaturated fatty acids, preferably omega-3 s.

Suitable omega-3 polyunsaturated fatty acids include docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), eicosatrienoic acid (ETE), hexadecatrienoic acid 16:3 (n-3), juniperonic acid (ETA), stearidonic acid (STD), tetracosahexaenoic acid, tetracosapentaenoic acid, a-linolenic acid (ALA), and mixtures thereof.

Within the scope of the invention, docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA) are preferred, DHA being the most preferred.

In some embodiments, the composition according to the invention may contain omega-3 lipid precursors or derivatives, such as resolvins, protectins, maresins and mixtures thereof or natural and synthetic intermediates.

It has been observed that the presence of omega-3 polyunsaturated fatty acids reduces the inflammatory processes that accompany cystic fibrosis.

In accordance with some preferred embodiments, the lipid composition comprises a combination of MCTs, preferably caprylic acid (C:8) and capric acid (C: 10), and polyunsaturated fatty acids, preferably omega-3, as described above, preferably DHA, preferably in a ratio of 7 to 11: 1, for example 9:1. In these proportions of the lipid components of the composition for the uses described herein, an unexpected increase in enteric absorption of the CFTR modulators described herein and an increased bioavailability and consequent unexpected greater therapeutic effect have been observed.

Advantageously, the percentage amount of MCT in the combination with omega-3s is comprised between 75% and 99.9% by weight, preferably between 80 and 95 by weight, for example 90% by weight, while that of omega-3 s, preferably DHA, is comprised between 0.1% and 25% by weight, preferably between 0.5% and 20% by weight, for example 10%.

Preferably, the composition contains MCTs from 80 to 95% by weight and polyunsaturated fatty acids from 0.5 to 20% by weight on the total weight of the lipid composition. Preferably, the lipid composition according to the invention, containing amounts of 10 to 20 g of lipids for each dose of drug administered in the case of adolescents and adults, and 5 to 10 g of lipids for each dose of drug administered in the case of children, enhances the absorption and efficacy of the CTFR modulators or correctors described herein.

In accordance with certain embodiments, the lipid composition according to the invention is administered simultaneously, separately or sequentially to the following CTFR modulators according to one of the following two therapeutic schemes:

Table 2, Dosage and administration of CFTR protein modulators/correctors.

The CTFR modulator/corrector dosage schemes according to Table 1 or 2, for simultaneous, separate or sequential use with a lipid composition according to any one of the embodiments described herein, represent preferred embodiments of the invention.

In accordance with certain aspects, a method is described herein for the treatment of cystic fibrosis in an individual in need of treatment comprising oral administration of an oral lipid composition according to any one of the embodiments described herein, preferably in a therapeutic regimen in combination with a mixture of the active ingredients Ivacaftor, Tezacaftor, Elexacaftor and/or Ivacaftor taken individually, separately or sequentially from the administration of the mixture of said active ingredients, preferably after 10-14 hours, more preferably 12 hours after their oral administration.

Preferably, the lipid composition is administered within one hour of taking the Kaftrio® drug in a therapeutic regimen that preferably provides for separate administration of Ivacaftor.

Administration of the lipid composition, concurrently with drug intake, provides an adequate amount of fat to ensure the highest possible degree of absorption and bioavailability of the drug(s) described herein.

In some embodiments, the composition according to the invention may further comprise biologically active substances or active ingredients.

For example, the composition may include one or more vitamins, for example group B vitamins, vitamin A, vitamin C, vitamin D, vitamin K, etc.

According to some embodiments, the composition according to the invention comprises micronutrients and/or minerals as corresponding anions or cations or in the form of salts.

Thus, in some embodiments there may be minerals selected from iron, zinc, manganese, copper, selenium, magnesium and mixtures thereof.

The compositions according to the invention are suitable for food, nutritional, dietary or pharmaceutical use in mammals, in particular humans.

In accordance with some embodiments, the lipid composition, for example, in the form of a dietary supplement or food for special medical purposes, may contain at least one physiologically acceptable or edible vehicle.

The composition according to the invention may assume a wide variety of forms of preparation, depending on the desired route of administration.

The composition according to the invention may be in solid, liquid or semi-liquid form and preferably is solid.

When the composition according to the invention is presented in solid form it may be in tablet, capsule, powder, granule, pill, and powder form and preferably is in granular or powder form, typically to be reconstituted in a liquid, for example water.

Preparations in solid form, for example of powder, may comprise one or more excipients/vehicles such as for example amides, sugars, microcrystalline cellulose and optionally diluents, granulation agents, lubricants, ligands, disintegration agents.

For example, the composition in solid form may contain a ligand such as gum tragacanth, gum, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegration agent such as corn starch, potato starch, alginic acid; a lubricant such as magnesium stearate; a sweetening agent such as saccharose, acesulfame K, lactose or saccharin, oil in powder form. In certain embodiments the composition described herein may contain an algae, or an extract, for example an edible oil.

According to some embodiments, the composition according to the invention contains a cellulose-based excipient comprising i) organic cellulose esters, for example selected from cellulose acetate, cellulose propionate, cellulose triacetate, cellulose acetate propionate, cellulose butyrate acetate, ii) inorganic cellulose esters selected, for example, from nitrocellulose, cellulose sulfate, iii) cellulose ethers selected from a) alkyl cellulose ethers selected, for example, from methyl cellulose, ethyl cellulose, ethyl methyl cellulose; b) hydroxyalkyl cellulose ethers selected from, for example, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxy ethyl cellulose, hydroxypropyl methyl cellulose, ethyl hydroxyethyl cellulose; c) carboxyalkyl cellulose, for example, carboxymethyl cellulose, their salts and mixtures thereof. In some embodiments, the cellulose-based excipients are cross-linked with physiologically acceptable cross-linking agents.

In some embodiments, the composition according to the invention furthermore comprises one or more additional components such as additives, fillers, stabilizers, emulsifiers, texturizers, film-forming agents, plasticizers, wetting agents and thickeners. There may also be flavoring agents, preservatives, coloring agents and the like in the composition.

The composition according to the invention may be in liquid form.

When the composition is in liquid form, it may be in the form of a suspension, emulsion, solution, oral spray. In such cases, the vehicle is liquid and can be selected for example among water, glycols, oils, alcohols and mixtures thereof.

Typically, when the formulation is in liquid form it may contain excipients such as saccharose as a sweetening agent, methyl- and propylparabens as preservatives, a coloring agent, and a flavoring agent such as cherry or orange flavor.

Combined compositions can be suitably presented in a single pharmaceutical form and prepared using any of the methods well known in the pharmaceutical or food background art.

In some embodiments, in the compositions according to the present invention, the medium-chain triglycerides and polyunsaturated fatty acids are formulated in a dosage unit, for example, packaged in a single-dose sachet.

In accordance with certain embodiments, the dosage unit, for example in sachet form, contains 7-9 g of medium-chain triglycerides and 1 g of polyunsaturated fatty acids, in particular omega-3 s, preferably DHA.

According to some embodiments, the lipid composition according to the invention is a food supplement, nutritional product, dietary product, or food for special medical purposes or it is contained therein.

Preferably, the composition according to the present invention is administered orally.

Preferably, for oral administration, the composition is in the form of a powder or granulate that can be added to water at the time of administration.

The actual amount administered and the rate and time course of administration will depend on the nature and severity of the cystic fibrosis to be treated. Prescription of treatment, for example, decisions on dosage, dilution, etc., ultimately fall under the responsibility of physicians or dietitians and is at their discretion, and typically takes into account the condition to be treated, the dosage of the CFTR modulating drugs, the individual subject's condition, the site of delivery, the method of administration, and other factors known to practitioners. The precise dose will depend on a series of factors, including the form of the composition to be administered.

In some embodiments, the composition is administered one or more times a day to a subject in need of treatment, for example concurrently with or one hour after the administration of Ivacaftor, Tezacaftor, Elexacaftor, mixtures thereof, and/or Ivacaftor on its own.

Unless otherwise defined, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art in the field of the present invention.

The term "CFTR protein modulator" as used herein does not comprise "CFTR protein inhibitors."

In particular, as used herein, the term "edible" means substances suitable to be eaten whose use in the formulation of a nutritional or food composition for oral administration is approved by health authorities.

A "physiologically acceptable" vehicle may be a pharmaceutically acceptable vehicle.

The term "vehicle" as used herein means a medium, excipient, or diluent by which the combination of active components of the formulation is administered.

The term "combination" referring to two or more components means that the components or ingredients are both present in the composition without interacting with each other chemically, for example to form a mixture without forming chemical bonds, such as covalent bonds, between the components of the mixture. In some embodiments, the composition comprises an edible and/or physiologically acceptable excipient or vehicle.

The composition described herein may be formulated with vehicles suitable for oral administration.

The biologically active substances such as medium- or long-chain fatty acids contained in the composition may be combined or mixed as active ingredients intimately admixed with an edible vehicle and/or excipient according to the pharmaceutical and food industry or according to traditional nutritional techniques.

Any vehicle and/or excipient suitable for the form of preparation that is desired for administration is admitted.

The following examples are given to illustrate the object of the invention.

EXAMPLE 1

A composition in pharmaceutical form of powder for use in the treatment of cystic fibrosis in patients using CFTR protein modulating drugs preferably selected from Ivacaftor, Tezacaftor and Elexacaftor and their mixtures (Kaftrio®/Trikafta®) having the following formulation (active ingredients expressed as g / 100 g and g / sachet of about 19 g):

*of which C:8 + C: 10 > 85% tot MCT

Ingredients: MCT-A70 (medium chain triglycerides, acacia gum, silicon dioxide), oil powder from Schizochy trium sp. algae (DHA), flavoring, maltodextrins, sweetener: acesulfame k. EXAMPLE 2

A composition in pharmaceutical form of powder packaged in a jar for use in the treatment of cystic fibrosis in patients using CFTR protein modulating drugs having the following formulation (active ingredients expressed as g / 100 g and g / scoop of about 9 g):

*of which C:8 + C: 10 > 85% tot MCT

Ingredients: MCT-A70 (medium-chain triglycerides, acacia gum, silicon dioxide), oil powder from Schizochy trium sp. algae (DHA), flavoring, maltodextrin, sweetener: acesulfame k.

Claims

1. An oral lipid composition comprising a combination of mediumchain fatty acids and long-chain polyunsaturated fatty acids for simultaneous, separate or sequential use with a CFTR protein modulator drug selected from Ivacaftor, Tezacaftor, Elexacaftor and mixtures thereof in the treatment of cystic fibrosis in a population of individuals aged 2 years or older with at least one F508 (F508del) mutation in the transmembrane conductance regulator gene, wherein the medium-chain fatty acids are MCT medium-chain triglycerides with 6-12 carbon atoms and the long-chain polyunsaturated fatty acids are omega-3.

2. The lipid composition for use according to claim 1, wherein said medium-chain fatty acids are MCT medium-chain triglycerides having 6 to 10 carbon atoms.

3. The lipid composition for use according to claim 2, wherein said MCT medium-chain triglycerides are caprylic acid (C:8) and capric acid (C: 10) and a mixture thereof.

4. The lipid composition for use according to any one of claims 1-3 wherein said omega-3 s are selected from docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), eicosapentaenoic acid (EP A), eicosatrienoic acid (ETE), hexadecatrienoic acid 16: 3 (n-3), juniperonic acid (ETA), stearidonic acid (STD), tetracosahexaenoic acid, tetracosapentaenoic acid, a-linolenic acid (ALA), and mixtures thereof.

5. The lipid composition for use according to claim 4, wherein the omega-3 acids are selected from docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), eicosapentaenoic acid (EP A) and mixtures thereof, preferably docosahexaenoic acid (DHA).

6. The lipid composition for use according to any one of claims 1-5, wherein the CFTR protein modulating drugs are selected from Ivacaftor, Tezacaftor, Elexacaftor, and mixtures thereof, preferably their mixture.

7. The lipid composition for use according to claim 6, wherein the CFTR protein modulators are a mixture of Ivacaftor, Tezacaftor, Elexacaftor for simultaneous, separate or sequential use with Ivacaftor.

8. The lipid composition for simultaneous, separate, or sequential use according to any one of claims 1-7 with two doses each containing 37.5 mg of Ivacaftor, two doses each containing 25 mg of Tezacaftor, two doses each containing 50 mg of Elexacaftor, said doses being administered in the morning, and a subsequent dose containing 75 mg of Ivacaftor, said dose being administered in the evening and wherein the treated individual has an age between 6 years and less than 12 and a body weight of less than 30 kg.

9. The lipid composition for simultaneous, separate or sequential use according to any one of claims 1-7 with two tablets each containing 75 mg of Ivacaftor, two tablets each containing 50 mg of Tezacaftor, two tablets each containing 100 mg of Elexacaftor, said tablets being administered in the morning, and subsequently one tablet containing 150 mg of Ivacaftor, said tablet being administered in the evening and where the treated individual is 12 years old or older or 6 to 12 years old and a body weight greater than or equal to 30 kg.

10. The oral lipid composition for simultaneous, separate or sequential use according to any one of claims 1-7 in combination with a CFTR protein modulator drug selected from Ivacaftor, Tezacaftor, Elexacaftor and mixtures thereof in the treatment of cystic fibrosis, preferably according to the following dosage scheme:

11. The composition for use according to any one of claims 1-10, wherein the MCT medium-chain triglycerides and the omega-3 long-chain polyunsaturated fatty acids are in a 7-11 :1, preferably 9:1, ratio.

12. The composition for use according to any one of claims 1-11, wherein the medium-chain triglycerides and the omega-3 long-chain polyunsaturated fatty acids are mixed so that the percentage quantity of medium-chain triglycerides is comprised from 75% to 99.9%, preferably 80 to 95% by weight, and the percentage quantity of omega-3 polyunsaturated fatty acids, preferably DHA, is comprised between 0.1% and 25% by weight, preferably 0.5 to 20% by weight.

13. The composition for use according to any one of claims 1-12 in liquid or solid form, preferably powder or granules.

14. The composition for use according to any one of claims 1-13, further comprising a vitamin, preferably selected from group B vitamins, vitamin C, vitamin D and mixtures thereof, and a mineral preferably as corresponding anions or cations or in the form of salts, preferably selected from iron, zinc, manganese, copper, selenium, magnesium, and mixtures thereof.

15. A dietary supplement or food for special medical purposes, comprising a composition for use according to any one of claims 1-14, preferably in the form of a sachet dosage unit, preferably containing 10-20 g of lipids or 5-10 g of lipids per dose of drug.

16. The dietary supplement or food for special medical purposes comprising a composition for use according to any one of claims 1-15, in the pharmaceutical form of a powder preferably packaged in a container or jar.